Tenaya Therapeutics Inc

Previous wording

In addition to historical financial information, this discussion and analysis and other parts of this report contain 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, based upon current expectations that involve risks, uncertainties and assumptions. Our actual results could differ materially from those anticipated in these forward-looking statements as a result of various factors, including those set forth in the section titled “Risk Factors” under Part II, Item 1A. below. You should carefully read the “Risk Factors” to gain an understanding of the factors that could cause actual results to differ materially from our forward-looking statements. Please also see the section titled “Special Note Regarding Forward-Looking Statements.”

Current wording

In addition to historical financial information, this discussion and analysis and other parts of this report contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the Securities Act), and Section 21E of the Securities Exchange Act of 1934, as amended, based upon current expectations that involve risks, uncertainties and assumptions. Our actual results could differ materially from those anticipated in these forward-looking statements as a result of various factors, including those set forth in the section titled “Risk Factors” under Part II, Item 1A. below. You should carefully read the “Risk Factors” to gain an understanding of the factors that could cause actual results to differ materially from our forward-looking statements. Please also see the section titled “Special Note Regarding Forward-Looking Statements.”

Previous wording

TN-201 is our potential first-in-class and best-in-class gene therapy for adults and children with HCM due to MYBPC3 gene mutations. These mutations result in a deficiency of myosin binding protein, which in turn can cause the heart walls of affected individuals to become significantly thickened, leading to fibrosis, abnormal heart rhythms, cardiac dysfunction and heart failure. HCM is a chronic, progressive condition and those diagnosed with the disease often experience significant impairment in overall quality of life. TN-201 utilizes a recombinant adeno-associated virus serotype 9 (AAV9) capsid to deliver a working MYBPC3 gene to specific cells of the heart in order to produce cardiac myosin binding protein and thereby slow or even reverse the course of MYBPC3-associated HCM following a single infusion. In October 2023, we began dosing patients in the MyPEAKTM-1 Phase 1b multi-center, open-label clinical trial, designed to assess the safety, tolerability and efficacy of a one-time intravenous infusion of TN-201. Initial data from the trial is anticipated in the second half of 2024.

Current wording

TN-201 is our potential first-in-class and best-in-class gene therapy for adults and children with HCM due to MYBPC3 gene mutations. These mutations result in a deficiency of myosin binding protein, which in turn can cause the heart walls of affected individuals to become significantly thickened, leading to fibrosis, abnormal heart rhythms, cardiac dysfunction and heart failure. HCM is a chronic, progressive condition and those diagnosed with the disease often experience significant impairment in overall quality of life and may be at higher risk for serious complications and co-morbidities. TN-201 utilizes a recombinant adeno-associated virus serotype 9 (AAV9) capsid to deliver a working MYBPC3 gene to specific cells of the heart in order to produce cardiac myosin binding protein and thereby slow or even reverse the course of MYBPC3-associated HCM following a single infusion. In October 2023, we began dosing patients in the MyPEAKTM-1 Phase 1b multi-center, open-label clinical trial, designed to assess the safety, tolerability and efficacy of a one-time intravenous infusion of TN-201. MyPEAK-1 is actively enrolling patients at several U.S. clinical sites and initial data from the trial is anticipated in the second half of 2024.

Previous wording

To support our development efforts for TN-201 we are conducting two noninterventional studies: a study evaluating seroprevalence to AAV9 antibodies among adults with MYBPC3-associated HCM, and MyClimb, a prospective and retrospective global natural history study focused on pediatric patients with MYBPC3 mutation-associated cardiomyopathy. The seroprevalence study has completed enrollment and data is under analysis. The objective of the natural history study is to characterize the outcomes, burden of illness, risk factors, quality of life, and biomarkers associated with disease progression in pediatric patients with cardiomyopathy due to MYBPC3 gene mutations, as well as treatments and procedures. MyClimb complements existing disease registries focused primarily on adult patient HCM populations and may support and expedite the development of TN-201 in the pediatric patient population. TN-201 has received orphan drug designation from the FDA and orphan medicinal product designation from the EC, as well as Fast Track Designation from the FDA.

Current wording

To support our development efforts for TN-201 we are conducting two noninterventional studies: a study evaluating seroprevalence to AAV9 antibodies among adults with MYBPC3-associated HCM, and MyClimb, a prospective and retrospective global natural history study focused on pediatric patients with MYBPC3 mutation-associated cardiomyopathy. The seroprevalence study has completed enrollment and data is under analysis. The objective of the natural history study is to characterize the outcomes, burden of illness, risk factors, quality of life, and biomarkers associated with disease progression in pediatric patients with cardiomyopathy due to MYBPC3 gene mutations, as well as treatments and procedures. MyClimb complements existing disease registries focused primarily on adult patient HCM populations and may support and expedite the development of TN-201 in the pediatric patient population. In July 2024, we received rare pediatric disease designation from the FDA for TN-201 in MYBPC3-associated HCM. TN-201 has also been granted orphan drug designation from the FDA, orphan medicinal product designation from the European Commission (EC), and Fast Track Designation from the FDA.

Previous wording

In October 2023, the FDA provided clearance of our IND application to initiate clinical testing of TN-401. We plan to initiate patient dosing in RIDGETM-1, our Phase 1b multi-center, open-label clinical trial, designed to assess the safety, tolerability and efficacy of a one-time intravenous infusion of TN-401, in the second half of 2024. In support of our development efforts for TN-401, we have initiated a global noninterventional study to collect treatment history and seroprevalence to AAV9 antibodies data among ARVC patients who carry pathogenic or likely pathogenic PKP2 gene mutations.TN-401 has received orphan drug designation from the FDA and orphan medicinal product designation from the European Commission (EC), as well as Fast Track Designation from the FDA.

Current wording

In support of our development efforts for TN-401, we have initiated a global noninterventional study to collect treatment history and seroprevalence to AAV9 antibodies data among ARVC patients who carry pathogenic or likely pathogenic PKP2 gene mutations.TN-401 has received orphan drug designation from the FDA and orphan medicinal product designation from the EC, as well as Fast Track Designation from the FDA.

Previous wording

TN-301 is our small molecule inhibitor of histone deacetylase-6 (HDAC6), initially being developed for the potential treatment of HFpEF. HFpEF is characterized by a stiffening of the heart muscle resulting in an inability for the left ventricle to relax and pump blood effectively with each contraction. There are several cellular processes thought to underlie the pathophysiology of HFpEF, including increases in fibrosis and inflammation and defects in metabolism. Although HFpEF accounts for approximately half of all heart failures, there are few proven treatment options.

Current wording

TN-301 is our small molecule inhibitor of histone deacetylase-6 (HDAC6), initially being developed for the potential treatment of HFpEF. HFpEF is characterized by a stiffening of the heart muscle resulting in an inability for the left ventricle to relax and fill with oxygenated blood sufficient to meet the body’s needs. There are several cellular processes thought to underlie the pathophysiology of HFpEF, including increases in fibrosis and inflammation and defects in metabolism. Although HFpEF accounts for approximately half of all heart failures, there are few proven treatment options.

Previous wording

In October 2023, we shared positive data from our Phase 1 clinical trial of TN-301 in healthy participants at the 2023 Heart Failure Society of America Annual Scientific Meeting. The Phase 1 trial enrolled participants in two stages. In Stage 1, participants received single ascending doses and in Stage 2, participants received multiple ascending doses. TN-301 was generally well tolerated across the broad range of doses studied. Pharmacokinetic results showed overall dose proportionality in both stages of the clinical trial with a half-life supportive of once-daily dosing. Increasing doses and exposures with TN-301 correlated with increased pharmacodynamic effects. There were no changes in histone acetylation with TN-301 underscoring the selectivity of TN-301 for HDAC6 and potentially reducing the risk of off target effects observed with less selective HDAC6 inhibitors or pan-HDAC inhibition. In preclinical studies, selective HDAC6 inhibition has been shown to have comparable efficacy to empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor which is approved for the treatment of HFpEF. More recently, using a validated mouse model of disease, we demonstrated that HDAC6 inhibition co-administered with a SGLT2 inhibitor demonstrated additive benefit, improving several measures of heart function. Taken together, these data support continued development of TN-301 as a potential treatment for patients with HFpEF. We believe late-stage clinical development of TN-301 is best suited for development by or with a well-resourced partner.

Current wording

In October 2023, we shared positive data from our Phase 1 clinical trial of TN-301 in healthy participants at the 2023 Heart Failure Society of America Annual Scientific Meeting. TN-301 was generally well tolerated across the broad range of doses studied. Pharmacokinetic results showed overall dose proportionality with a half-life supportive of once-daily dosing. Increasing doses and exposures with TN-301 correlated with increased pharmacodynamic effects. There were no changes in histone acetylation with TN-301 underscoring the selectivity of TN-301 for HDAC6 and potentially reducing the risk of off target effects. In preclinical studies, selective HDAC6 inhibition has been shown to have comparable efficacy to empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor which is approved for the treatment of HFpEF and co-administration of our HDAC6 inhibition with a SGLT2 inhibitor demonstrated additive benefit. Taken together, these data support continued development of TN-301 as a potential treatment for patients with HFpEF. We believe late-stage clinical development of TN-301 is best suited for development by or with a well-resourced partner.

Previous wording

In May 2024, we announced cost containment measures, including a committed plan to reduce our workforce (the “Workforce Reduction”) by approximately 22%. The cost containment measures align with our focus on generating data from our clinical-stage gene therapy programs.

Current wording

In May 2024, we announced cost containment measures, including a committed plan to reduce our workforce (the Workforce Reduction) by approximately 22%, which was substantially completed in the second quarter of

Previous wording

a decrease of $2.2 million in facility and laboratory costs, reflecting lower costs for laboratory supplies and materials related to IND-enabling activities; partially offset by

Current wording

a decrease of $2.5 million in facility and laboratory costs, reflecting lower facility management fees and lower costs of supplies and materials as there were no IND-enabling activities in 2024; and

Previous wording

an increase of $1.0 million in employee-related costs reflecting higher stock-based compensation and salaries; and

Current wording

an increase of $1.0 million in employee-related costs primarily driven by employee severance and continuing health insurance costs from the Workforce Reduction and higher stock-based compensation and salaries.

Previous wording

Interest income primarily consists of interest earned on our cash, cash equivalents and investment balances. The year-over-year decrease of $0.5 million was primarily due to lower cash, cash equivalents and investment balances.

Current wording

Interest income primarily consists of interest earned on our cash, cash equivalents and investment balances. The year-over-year decrease of $0.4 million was primarily due to lower cash, cash equivalents and investment balances.

Previous wording

Net loss for the three months ended March 31, 2024, was $32.2 million, compared to a net loss of $31.7 million for the three months ended March 31, 2023.

Current wording

Net loss for the three months ended June 30, 2024, was $29.4 million, compared to a net loss of $33.3 million for the three months ended June 30, 2023.

Previous wording

Since our inception, we have not generated any revenue and we have incurred significant net losses and negative cash flows from operations. From our inception through March 31, 2024, we have funded our operations primarily from the sale and issuance of our equity securities. As of March 31, 2024, we had cash, cash equivalents and investments in marketable securities of $122.2 million and an accumulated deficit of $435.5 million.

Current wording

Since our inception, we have not generated any revenue and we have incurred significant net losses and negative cash flows from operations. From our inception through June 30, 2024, we have funded our operations primarily from the sale and issuance of our equity securities. As of June 30, 2024, we had cash, cash equivalents and investments in marketable securities of $99.3 million and an accumulated deficit of $464.9 million.

Previous wording

Net cash used in operating activities for the three months ended March 31, 2024 was $28.7 million, which consisted primarily of a net loss of $32.2 million and a net change in operating assets and liabilities of $3.6 million, partially offset by $6.9 million in non-cash charges. The change in net operating assets and liabilities was primarily due to a decrease in accounts payable and accrued expenses and other current liabilities of $3.1 million and a decrease in operating lease liabilities of $1.1 million, partially offset by a decrease of prepaid expenses and other current assets of $0.4 million. Cash flows from operations are generally impacted by the timing of payments to vendors and vendor payment terms. The non-cash charges primarily consisted of stock-based compensation of $4.2 million and depreciation and amortization of $2.2 million.

Current wording

Net cash used in operating activities for the six months ended June 30, 2024 was $52.3 million, which consisted primarily of a net loss of $61.7 million and a net change in operating assets and liabilities of $5.6 million, partially offset by $14.2 million in non-cash charges. The change in net operating assets and liabilities was primarily due to a decrease in accounts payable and accrued expenses and other current liabilities of $4.9 million and a decrease in operating lease liabilities of $2.2 million, partially offset by a decrease of prepaid expenses and other current assets of $1.1 million. Cash flows from operations are generally impacted by the timing of payments to vendors and vendor payment terms. The non-cash charges primarily consisted of stock-based compensation of $8.8 million and depreciation and amortization of $4.3 million.

Previous wording

Net cash used in operating activities for the three months ended March 31, 2023 was $30.3 million, which consisted primarily of a net loss of $31.7 million and a net change in operating assets and liabilities of $4.4 million, partially offset by $5.9 million in non-cash charges. The change in net operating assets and liabilities was primarily due to a decrease in accounts payable and accrued expenses and other current liabilities of $4.0 million and a decrease in operating lease liabilities of $1.0 million. Cash flows from operations are generally impacted by the timing of payments to vendors and vendor payment terms. The non-cash charges primarily consisted of stock-based compensation of $3.5 million and depreciation and amortization of $2.1 million.

Current wording

Net cash used in operating activities for the six months ended June 30, 2023 was $56.5 million, which consisted primarily of a net loss of $65.0 million and a net change in operating assets and liabilities of $3.8 million, partially offset by $12.2 million in non-cash charges. The change in net operating assets and liabilities was primarily due to a decrease in operating lease liabilities of $2.0 million and a decrease in accounts payable and accrued expenses and other current liabilities of $1.8 million. Cash flows from operations are generally impacted by the timing of payments to vendors and vendor payment terms. The non-cash charges primarily consisted of stock-based compensation of $7.3 million and depreciation and amortization of $4.3 million.

Previous wording

Net cash provided by investing activities for the three months ended March 31, 2023 was $8.1 million, which consisted of proceeds from maturities of marketable securities of $34.5 million, partially offset by purchases of marketable securities of $25.8 million.

Current wording

Net cash provided by investing activities for the six months ended June 30, 2024 was $17.1 million, which consisted primarily of proceeds from maturities of marketable securities of $52.2 million, partially offset by purchases of marketable securities of $34.5 million.

Previous wording

Net cash used in investing activities for the three months ended March 31, 2024 was $4.5 million, which consisted primarily of purchases of marketable securities of $23.6 million, partially offset by proceeds from maturities of marketable securities of $19.7 million.

Current wording

Net cash provided by investing activities for the six months ended June 30, 2023 was $33.1 million, which consisted primarily of proceeds from maturities of marketable securities of $75.0 million, partially offset by purchases of marketable securities of $41.0 million.

Previous wording

Net cash provided by financing activities for the three months ended March 31, 2024 was $46.8 million, which primarily consisted of net proceeds from follow-on offering of $46.8 million.

Current wording

Net cash provided by financing activities for the six months ended June 30, 2024 was $47.3 million, which primarily consisted of net proceeds from follow-on offering of $46.8 million.

Previous wording

Net cash used in financing activities for the three months ended March 31, 2023 consisted of payments of accrued offering costs.

Current wording

Net cash provided by financing activities for the six months ended June 30, 2023 was $3.7 million, which primarily consisted of proceeds from at-the-market sales of $3.9 million, partially offset by payments of accrued offering costs.

Previous wording

A summary of our critical accounting policies and estimates is presented in Part II, Item 7 of our Annual Report on Form 10-K for the year ended December 31, 2023. There were no material changes to our critical accounting policies and estimates during the three and three months ended March 31, 2024.

Current wording

A summary of our critical accounting policies and estimates is presented in Part II, Item 7 of our Annual Report on Form 10-K for the year ended December 31, 2023. There were no material changes to our critical accounting policies and estimates during the three and six months ended June 30, 2024.