26 unchanged sentences
We recently completed a commercially representative GMP batch of TSHA-120 which demonstrated that the pivotal lots from the commercial grade material were generally analytically comparable to the original clinical trial material.
−Removed: Release testing for this batch is currently underway and expected to be completed in September 2022.
−Removed: Additional discussions with Health Authorities are planned to discuss these comparability data and a potential registration pathway with feedback anticipated by the end of 2022.
−Removed: For Rett syndrome, we submitted a Clinical Trial Application, or CTA, filing to Health Canada in November 2021 and announced initiation of clinical development of TSHA-102 under the approved CTA in March 2022.
−Removed: We expect to report preliminary clinical data for TSHA-102 in Rett syndrome by year-end 2022.
+Added: Release testing for this batch is currently underway and expected to be completed in the fourth quarter of 2022.
+Added: Additional discussions with Health Authorities are planned to discuss these comparability data and a potential registration pathway.
+Added: In September 2022, we submitted a meeting request to the FDA and were granted a Type B end-of-Phase 2 meeting via teleconference on December 13, 2022.
+Added: We expect to provide an update on the feedback from the FDA following receipt of the formal Type B end-of-Phase 2 meeting minutes, anticipated in mid-January 2023.
+Added: For Rett syndrome, we submitted a Clinical Trial Application, or CTA, filing to Health Canada in November 2021 and announced initiation of clinical development of TSHA-102 under the approved CTA in
+Added: We expect to report preliminary safety and efficacy data for TSHA-102 from the entire first cohort of adult patients with Rett syndrome in the first half of 202 3 .
+Added: We also expect to initiate a female pediatric clinical trial in the first half of 2023.
We recently executed an exclusive option from UT Southwestern to license worldwide rights to a clinical-stage CLN7 program.
−Removed: The CLN7 program is currently in a Phase 1 clinical
−Removed: proof-of-concept trial run by UT Southwestern, and we reported preliminary clinical safety data for the first patient in history to be intrathecally dosed at 1.0x10 15 total vg with the first-generation construct in December 2021.
+Added: The CLN7 program is currently in a Phase 1 clinical proof-of-concept trial run by UT Southwestern, and we reported preliminary clinical safety data for the first patient in history to be intrathecally dosed at 1.0x10 15 total vg with the first-generation construct in December 2021.
Development of the CLN7 program will continue in collaboration with existing partners with future clinical development to focus on the first-generation construct.
4 unchanged sentences
We do not have any product candidates approved for sale and have not generated any revenue from product sales.
−Removed: We have funded our operations primarily through the sale of equity, raising an aggregate of $319.0 million of gross proceeds from our initial public offering and private placements of our convertible preferred stock as well as sales of common stock pursuant to our Sales Agreement (as defined below).
−Removed: In addition, we drew down $30.0 million and $10.0 million in term loans on August 12, 2021 and December 29, 2021, respectively.
+Added: We have funded our operations primarily through the sale of equity, raising an aggregate of $434.0 million of gross proceeds from our initial public offering, sales of common stock pursuant to our Sales Agreement (as defined below) and our October 2022 follow-on offering, pre-IPO private placements of our convertible preferred stock, from our Term Loan Agreement (as defined below) and from the Astellas Transactions.
On August 12, 2021, or the Closing Date, we entered into a Loan and Security Agreement, or the Term Loan Agreement, with the lenders party thereto from time to time, or the Lenders and Silicon Valley Bank, as administrative agent and collateral agent for the Lenders, or the Agent.
1 unchanged sentence
We drew $30.0 million in term loans on the Closing Date and drew an additional $10.0 million term loan on December 29, 2021.
+Added: We did not draw the additional $20.0 million tranche prior to its expiration on September 30, 2022.
The loan repayment schedule provides for interest only payments until August 31, 2024, followed by consecutive monthly payments of principal and interest.
1 unchanged sentence
Since our inception, we have incurred significant operating losses.
−Removed: Our net losses were $84.0 million for the six months ended June 30, 2022 and $73.0 million for the six months ended June 30, 2021.
−Removed: As of June 30, 2022, we had an accumulated deficit of $319.6 million.
+Added: Our net losses were $110.3 million for the nine months ended September 30, 2022 and $124.1 million for the nine months ended September 30, 2021.
+Added: As of September 30, 2022, we had an accumulated deficit of $345.9 million.
We expect to continue to incur significant expenses and operating losses for the foreseeable future.
29 unchanged sentences
This phenotype represents up to 6% of all CMT2 diagnosis.
−Removed: In the late-onset population, patients have poor quality of life but the disease is not life-limiting.
+Added: In the late-onset population, patients have poor quality of life, significantly compromised activities of daily living, and is life limiting but not as severely as classic GAN.
In early-onset disease, symptomatic treatments attempt to maximize physical development and minimize the rate of deterioration.
131 unchanged sentences
DNA are nearly identical and provided further support that for a conclusion that the nature of our product is unchanged between our early clinical and pivotal batches as noted in the below pie charts.
−Removed: The TSHA-120 pivotal lot, which yielded over 50 patient doses of TSHA-120 at the highest dose cohort of 3.5E14 total vg, is expected to complete quality release testing by end of the third quarter of 2022.
+Added: The TSHA-120 pivotal lot, which yielded over 50 patient doses of TSHA-120 at the highest dose cohort of 3.5E14 total vg, is currently expected to complete quality release testing in November 2022.
This material positions us for future BLA-enabling activities and commercial production.
1 unchanged sentence
In September 2021, we submitted a request for a Scientific Advice meeting for TSHA-120 to the United Kingdom’s Medicines and Healthcare products Regulatory Agency, or MHRA, and were granted a meeting in January 2022.
−Removed: MHRA agreed on our commercial manufacturing and release assay testing strategy including potency assays and we plan to dose a few additional patients with commercial grade material, which will be released in September 2022.
+Added: MHRA agreed on our commercial manufacturing and release assay testing strategy including potency assays and we plan to dose a few additional patients with commercial grade material, which will be released in November 2022.
Finally, MHRA was supportive of our proposal to perform validation work on MFM32 for GAN as a key clinical endpoint and for us to explore the MFM32 items with patients and families as part of this process.
−Removed: Given the positive comparability data for TSHA-120 that we recently received, additional discussions with Health Authorities to discuss these data and potential registration pathway are planned with regulatory feedback anticipated by year-end 2022.
+Added: Given the positive comparability data for TSHA-120 that we recently received, additional discussions with Health Authorities to discuss these data and a potential registration pathway are planned.
+Added: In September 2022, we submitted a meeting request to the FDA and were granted a Type B end-of-Phase 2 meeting via teleconference scheduled for December 13, 2022.
+Added: We expect to provide an update on the feedback from the FDA following receipt of the formal Type B end-of-Phase 2 meeting minutes, anticipated in mid-January 2023.
TSHA-102 for Rett Syndrome
13 unchanged sentences
Mice were subjected to phenotypic scoring and a battery of tests including gait, hindlimb clasping, tremor and others to comprise an aggregate behavioral score.
−Removed: miRARE attenuated
−Removed: miniMECP2-mediated aggravation in wild type aggregate phenotype severity scores.
+Added: miRARE attenuated miniMECP2-mediated aggravation in wild type aggregate phenotype severity scores.
Mice were scored on an aggregate severity scale using an established protocol.
12 unchanged sentences
Treatment with TSHA-102 significantly improved body weight, motor function and respiratory assessments in MECP2 knockout mice.
−Removed: An additional study in neonatal mice is ongoing, and preliminary data suggest normalization of survival.
−Removed: Finally, an IND/CTA-enabling 6-month Good Laboratory Practice, or GLP, toxicology study (n=24) examined the biodistribution, toxicological effects and mechanism of action of TSHA-102 when intrathecally administered to Non-Human Primates, or NHPs, across three dose levels.
+Added: Finally, an IND/CTA-enabling 6-month Good Laboratory Practice, or GLP, toxicology study (n=24) examined the biodistribution, toxicological effects and mechanism of action of TSHA-102 when intrathecally administered to Non-Human Primates,
+Added: or NHPs, across three dose levels.
Biodistribution, as reflected by DNA copy number, was observed in multiple areas of the brain, sections of spinal cord and the DRG.
Importantly, mRNA levels across multiple tissues were low, indicating miRARE regulation is minimizing transgene expression from the construct in the presence of endogenous MECP2 as expected, despite the high levels of DNA that were delivered.
−Removed: No toxicity from
−Removed: transgene overexpression was observed, confirmed by functional and histopathologic evaluations demonstrating no detrimental change in neurobehavioral assessments and no adverse tissue findings on necropsy.
+Added: No toxicity from transgene overexpression was observed, confirmed by functional and histopathologic evaluations demonstrating no detrimental change in neurobehavioral assessments and no adverse tissue findings on necropsy.
In neonatal knockout Rett mice, treatment with TSHA-102 resulted in near normalization of survival as shown below.
7 unchanged sentences
Safety and biodistribution assessments in NHPs were presented in May 2022 at the International Rett Syndrome Foundation (IRSF) meeting along with the caregiver perspective on Rett syndrome in adulthood.
−Removed: At the ASCEND National Summit, there was an oral presentation on “Putting Patients at the Center.” Finally, mouse pharmacology, rat and NHP toxicology data were presented at the 25th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT).
+Added: At the ASCEND National Summit, there was an oral presentation on “Putting Patients at the Center.” Finally, mouse pharmacology, rat and NHP toxicology data were presented at the 25th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT) and the European Society for Gene and Cell Therapy Congress (ESGCT).
We submitted a CTA for TSHA-102 in November 2021 and announced initiation of clinical development under a CTA approved by Health Canada in March 2022.
6 unchanged sentences
Elsa Rossignol, Assistant Professor Neuroscience and Pediatrics, and Principal Investigator.
−Removed: We expect to report preliminary clinical data for TSHA-102 in Rett syndrome by year-end 2022.
+Added: We expect to report preliminary clinical data for TSHA-102 from the entire first cohort of adult patients with Rett syndrome in the first half of 2023.
+Added: We also expect to initiate a female pediatric clinical trial in the first half of 2023.
We have received orphan drug designation and rare pediatric disease designation from the FDA and orphan drug designation from the European Commission for TSHA-102 for the treatment of Rett syndrome.
TSHA-118 for CLN1 Disease
−Removed: The first-generation construct for the CLN7 program was developed in the laboratory of Steven Gray, Ph.D., Associate Professor at UT Southwestern Medical Center and our Chief Scientific Advisor with financial support from Mila’s Miracle and Batten Hope, the leading CLN7 patient advocacy groups.
−Removed: We provided a grant to Batten Hope to support patient awareness, disease education and newborn screening initiatives.
−Removed: We recently executed an exclusive option from UT Southwestern to license worldwide rights to a clinical-stage CLN7 program.
−Removed: The CLN7 program is currently in a Phase 1 clinical proof-of-concept trial run by UT Southwestern, and we reported preliminary clinical safety data for the first patient in history to be intrathecally dosed at 1.0E15 total vg with the first-generation construct in December 2021.
−Removed: Development of the CLN7 program will continue in collaboration with existing partners with future clinical development to focus on the first-generation construct.
−Removed: CLN7 disease is a rare, fatal and rapidly progressive neurodegenerative disease that is a form of Batten disease.
−Removed: CLN7 is caused by autosomal recessive mutations in the MFSD8 gene that results in lysosomal dysfunction.
−Removed: Disease onset occurs around two to five years of age, with death often ensuing in young adolescence.
−Removed: Patients experience gradual nerve cell loss in certain parts of the brain and typically present with seizures, vision loss, speech impairment and mental and motor regression.
−Removed: Currently, there are no approved therapies to treat CLN7 disease, which impacts an estimated 4,000 patients globally.
−Removed: Preclinical data in rodents supported advancement of the first-generation construct into a Phase 1 clinical proof-of-concept study in patients with CLN7 disease.
−Removed: In an in vivo efficacy study, IT administration of the first-generation construct to MFSD8 knockout mice with high or low doses resulted in clear age and dose effects with early intervention and high dose achieving the best therapeutic benefits.
−Removed: IT high dose of the first-generation construct in younger knockout mice resulted in:
−Removed: 1) widespread MFSD8 mRNA expression in all tissues assessed;
−Removed: 2) nearly complete normalization of impaired open field and rotarod performance at 6 and 9 months post injection;
−Removed: 3) more than doubled
−Removed: median life expectancy (16.82 months versus 7.77 months in untreated knockout mice);
−Removed: and 4) maintenance of healthy body weight for a prolonged period of time.
−Removed: Toxicology studies in wild type rodents demonstrated safety and tolerability of IT administration of the first-generation construct.
−Removed: Clinical safety data presented at WORLDSymposium in February 2022 for the first-generation construct from the ongoing clinical trial following IT administration further demonstrated that the first-generation construct was well-tolerated at multiple doses including 1.0E15 total vg, which is the highest dose administered in humans ever for a gene therapy product.
−Removed: No adverse immune responses were noted, including no evidence of dorsal root ganglion toxicity or brain inflammation across all subjects.
−Removed: Moreover, stabilization in sural nerve conduction supported the absence of dorsal root ganglia inflammation.
−Removed: The ongoing trial includes three patients dosed to date, with two patients treated at the highest dose of 1.0Ex15 total vg.
−Removed: Complete blood counts revealed no signs of bone marrow suppression or clinically significant bone marrow reactivity, and CSF analysis revealed no signs of pleocytosis.
−Removed: A fourth patient was recently dosed at 1.0E15 total vg in March 2022.
−Removed: TSHA-118 for CLN1 Disease
CLN1 disease (one of the forms of Batten disease), a lysosomal storage disorder, is a progressive, fatal neurodegenerative disease with early childhood onset that has an estimated incidence of approximately 1 in 138,000 live births worldwide.
5 unchanged sentences
Late-infantile-onset CLN1 disease begins between two to four years of age with initial visual and cognitive decline followed by the development of ataxia and myoclonus, or quick, involuntary muscle jerks.
−Removed: Juvenile-onset CLN1 disease patients present between the ages of five to ten years old, with vision loss as a first symptom followed by cognitive decline, seizures and motor decline.
+Added: Juvenile-onset CLN1 disease patients present between the
+Added: ages of five to ten years old, with vision loss as a first symptom followed by cognitive decline, seizures and motor decline.
Approximately 60% of the children diagnosed with CLN1 disease in the United States present with early-onset infantile forms, with the remaining 40% experiencing later-onset childhood forms.
11 unchanged sentences
To date, all tested mutations result in no or a greatly reduced amount of the citrate in the cells.
−Removed: Diminished NaCT
−Removed: function leads to loss of neuronal uptake of citrate and other metabolites such as succinate that are critical to brain energy metabolism and function.
+Added: Diminished NaCT function leads to loss of neuronal uptake of citrate and other metabolites such as succinate that are critical to brain energy metabolism and function.
Affected children have impairments in gross motor function and speech production with relative preservation of fine motor skills and receptive speech.
5 unchanged sentences
We expect to initiate clinical development on TSHA-105 in SLC13A5 deficiency.
+Added: TSHA-121 for CLN7 Disease
+Added: The first-generation construct for the CLN7 program was developed in the laboratory of Steven Gray, Ph.D., Associate Professor at UT Southwestern Medical Center and our Chief Scientific Advisor with financial support from Mila’s Miracle and Batten Hope, the leading CLN7 patient advocacy groups.
+Added: We provided a grant to Batten Hope to support patient awareness, disease education and newborn screening initiatives.
+Added: We recently executed an exclusive option from UT Southwestern to license worldwide rights to a clinical-stage CLN7 program.
+Added: The CLN7 program is currently in a Phase 1 clinical proof-of-concept trial run by UT Southwestern, and we reported preliminary clinical safety data for the first patient in history to be intrathecally dosed at 1.0E15 total vg with the first-generation construct in December 2021.
+Added: Development of the CLN7 program will continue in collaboration with existing partners with future clinical development to focus on the first-generation construct.
+Added: CLN7 disease is a rare, fatal and rapidly progressive neurodegenerative disease that is a form of Batten disease.
+Added: CLN7 is caused by autosomal recessive mutations in the MFSD8 gene that results in lysosomal dysfunction.
+Added: Disease onset occurs around two to five years of age, with death often ensuing in young adolescence.
+Added: Patients experience gradual nerve cell loss in certain parts of the brain and typically present with seizures, vision loss, speech impairment and mental and motor regression.
+Added: Currently, there are no approved therapies to treat CLN7 disease, which impacts an estimated 4,000 patients globally.
+Added: Preclinical data in rodents supported
+Added: advancement of the first-generation construct into a Phase 1 clinical proof-of-concept study in patients with CLN7 disease.
+Added: In an in vivo efficacy study, IT administration of the first-generation construct to MFSD8 knockout mice with high or low doses resulted in clear age and dose effects with early intervention and high dose achieving the best therapeutic benefits.
+Added: IT high dose of the first-generation construct in younger knockout mice resulted in:
+Added: 1) widespread MFSD8 mRNA expression in all tissues assessed;
+Added: 2) nearly complete normalization of impaired open field and rotarod performance at 6 and 9 months post injection;
+Added: 3) more than doubled median life expectancy (16.82 months versus 7.77 months in untreated knockout mice);
+Added: and 4) maintenance of healthy body weight for a prolonged period of time.
+Added: Toxicology studies in wild type rodents demonstrated safety and tolerability of IT administration of the first-generation construct.
+Added: Clinical safety data presented at WORLDSymposium in February 2022 for the first-generation construct from the ongoing clinical trial following IT administration further demonstrated that the first-generation construct was well-tolerated at multiple doses including 1.0E15 total vg, which is the highest dose administered in humans ever for a gene therapy product.
+Added: No adverse immune responses were noted, including no evidence of dorsal root ganglion toxicity or brain inflammation across all subjects.
+Added: Moreover, stabilization in sural nerve conduction supported the absence of dorsal root ganglia inflammation.
+Added: The ongoing trial includes three patients dosed to date, with two patients treated at the highest dose of 1.0Ex15 total vg.
+Added: Complete blood counts revealed no signs of bone marrow suppression or clinically significant bone marrow reactivity, and CSF analysis revealed no signs of pleocytosis.
+Added: A fourth patient was recently dosed at 1.0E15 total vg in March 2022.
License Agreements
14 unchanged sentences
In connection with the Queen’s University Agreement, we paid Queen’s University a one-time fee of $3.0 million as an upfront fee and approximately $0.2 million to reimburse Queen’s University for certain plasmid production costs.
−Removed: We are obligated to pay Queen’s University up to $10.0 million in the aggregate upon achievement of certain regulatory milestones and up to $10.0 million in the aggregate upon achievement of certain commercial milestones, a low single digit royalty on net sales of licensed products, subject to certain customary reductions, and a percentage of non-royalty sublicensing revenue ranging in the low double digits.
+Added: We are obligated to pay Queen’s University up to $10.0 million in the aggregate upon achievement of certain regulatory milestones and up to $10.0 million in the aggregate upon achievement of certain commercial milestones, a low single digit royalty on net sales of licensed
+Added: products, subject to certain customary reductions, and a percentage of non-royalty sublicensing revenue ranging in the low double digits.
Royalties are payable on a licensed product-by-licensed product basis and country-by-country basis until expiration of the last valid claim of a licensed patent covering such licensed product in such country and the expiration of any regulatory exclusivity for such licensed product in such country.
−Removed: Additionally, we are obligated to pay Queen’s University a low double-digit portion of any
−Removed: amounts received by us in connection with the sale of a priority review voucher related to a licensed product, not to exceed a low eight-figure amount.
+Added: Additionally, we are obligated to pay Queen’s University a low double-digit portion of any amounts received by us in connection with the sale of a priority review voucher related to a licensed product, not to exceed a low eight-figure amount.
In connection with a separate research grant agreement with Queen’s University, we reimbursed Queen’s University for certain manufacturing production costs totaling $3.8 million in fiscal year 2020.
−Removed: No additional milestone payments were made in connection with the Queen’s University Agreement during the six months ended June 30, 2022.
+Added: No additional milestone payments were made in connection with the Queen’s University Agreement during the nine months ended September 30, 2022.
License Agreement with Abeona (CLN1 Disease)
6 unchanged sentences
In December 2021 the Company’s CTA filing for TSHA-118 for the treatment of CLN1 disease was approved by Health Canada and therefore triggered a regulatory milestone payment in connection with the Abeona CLN1 Agreement, and therefore we recorded $3.0 million within research and development expenses in the consolidated statements of operations for the year ended December 31, 2021.
−Removed: The milestone fee was paid in January 2022 and has been classified as an investing outflow in the condensed consolidated statements of cash flows for the six months ended June 30, 2022.
−Removed: No additional milestone payments were made or triggered during the six months ended June 30, 2022.
+Added: The milestone fee was paid in January 2022 and has been classified as an investing outflow in the condensed consolidated statements of cash flows for the nine months ended September 30, 2022.
+Added: No additional milestone payments were made or triggered during the nine months ended September 30, 2022.
The Abeona CLN1 Agreement expires on a country-by-country and licensed product-by-licensed product basis upon the expiration of the last royalty term of a licensed product.
6 unchanged sentences
We are obligated to pay Abeona up to $26.5 million in regulatory-related milestones and up to $30.0 million in sales-related milestones per licensed product and high single-digit royalties on net sales of licensed products.
−Removed: Royalties are payable on a licensed product-by-licensed product and country-by-country basis until the latest of the expiration or revocation or complete rejection of the last licensed patent covering such licensed product in the country where the licensed product is sold, the loss of market exclusivity in such country where the product is sold, or, if no licensed product exists in such country and no market exclusivity exists in such country, ten years from first commercial sale of such licensed product in such country.
+Added: Royalties are payable on a
+Added: licensed product-by-licensed product and country-by-country basis until the latest of the expiration or revocation or complete rejection of the last licensed patent covering such licensed product in the country where the licensed product is sold, the loss of market exclusivity in such country where the product is sold, or, if no licensed product exists in such country and no market exclusivity exists in such country, ten years from first commercial sale of such licensed product in such country.
In March 2022, our CTA filing for TSHA-102 for the treatment of Rett Syndrome was approved by Health Canada and therefore triggered a regulatory milestone payment in connection with the Rett Agreement.
−Removed: We recorded $1.0 million within research and development expenses in the condensed consolidated statements of operations for the six months ended June 3 0 , 2022.
−Removed: This milestone fee was not paid as of June 3 0, 2022 and has been recorded in accrued expenses and other current liabilities.
−Removed: This milestone fee was paid in July 2022.
+Added: We recorded $1.0 million within research and development expenses in the condensed consolidated statements of operations for the nine months ended September 30, 2022.
+Added: This milestone fee was paid in July 2022 and has been classified as an investing outflow in the condensed consolidated statements of cash flows for the nine months ended September 30, 2022.
The Abeona Rett Agreement expires on a country-by-country and licensed product-by-licensed product basis upon the expiration of the last royalty term of a licensed product.
1 unchanged sentence
We may terminate the agreement for convenience.
−Removed: Impact of COVID-19 on Our Business
+Added: Impacts of COVID-19 and Market Conditions on Our Business
We have been actively monitoring the COVID-19 situation and its impact globally.
−Removed: We believe our financial results for the six months ended June 30, 2022 were not significantly impacted by COVID-19.
−Removed: We believe our hybrid and remote working arrangements have had limited impact on our ability to maintain internal operations during the six months ended June 30, 2022.
−Removed: The extent to which COVID-19 may impact our business and operations will depend on future developments that are highly uncertain and cannot be predicted with confidence, such as the duration of the outbreak, the effectiveness of actions to contain and treat COVID-19, the efficacy, availability and adoption of vaccines and other treatments, both domestically and globally, and the impact of new variants or mutations of the coronavirus, such as the Delta and Omicron variants.
−Removed: Although we have not experienced any material business shutdowns or interruptions due to the COVID-19 pandemic, we cannot predict the scope and severity of any potential business shutdowns or disruptions in the future, including to our planned clinical trials and preclinical studies.
−Removed: Any such shutdowns or other business interruptions could result in material and negative effects to our ability to conduct our business in the manner and on the timelines presently planned, which could have a material adverse impact on our business, results of operation and financial condition.
+Added: We believe our financial results for the nine months ended September 30, 2022 were not significantly impacted by COVID-19.
+Added: We believe our hybrid and remote working arrangements have had limited impact on our ability to maintain internal operations during the nine months ended September 30, 2022.
Further, disruption of global financial markets and a recession or market correction, including as a result of the COVID-19 pandemic, the ongoing military conflict between Russia and Ukraine and the related sanctions imposed against Russia, and other global macroeconomic factors such as inflation, could reduce the Company’s ability to access capital, which could in the future negatively affect the Company’s liquidity and could materially affect the Company’s business and the value of its common stock.
20 unchanged sentences
Clinical and preclinical development timelines, the probability of success and development costs can differ materially from expectations.
−Removed: Due to the strategic reprioritization of programs and reduction in force announced in March 2022, we expect overall lower research and development expenses for the remainder of 2022 compared to 2021.
−Removed: We expect lower expenses for the remainder of 2022 as certain programs have been deprioritized.
+Added: Due to the strategic reprioritization of programs and reduction in force announced in March 2022, we expect overall lower research and development expenses for the second half of 2022 compared to 2021.
Our future expenses may vary significantly each period based on factors such as:
12 unchanged sentences
the ability to manufacture of our product candidates;
−Removed: regulators or institutional review boards, or IRBs requiring that we or our investigators suspend or terminate clinical development for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks;
+Added: regulators or institutional review boards requiring that we or our investigators suspend or terminate clinical development for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks;
the efficacy and safety profile of our product candidates.
5 unchanged sentences
Results of Operations
−Removed: Results of Operations for the Three Months ended June 30, 2022 and 2021
−Removed: The following table summarizes our results of operations for the three months ended June 30, 2022 and 2021 (in thousands):
−Removed: For the Three Months Ended June 30,
+Added: Results of Operations for the Three Months ended September 30, 2022 and 2021
+Added: The following table summarizes our results of operations for the three months ended September 30, 2022 and 2021 (in thousands):
+Added: For the Three Months Ended September 30,
Operating expenses:
9 unchanged sentences
Research and Development Expenses
−Removed: Research and development expenses were $23.1 million for the three months ended June 30, 2022, compared to $30.6 million for the three months ended June 30, 2021.
−Removed: The $7.5 million decrease was primarily attributable to a decrease of $3.8 million in third-party research and development primarily related to GLP toxicology studies, a decrease of $3.2 million in research and development manufacturing, and lower employee compensation expenses of $0.5 million.
+Added: Research and development expenses were $16.4 million for the three months ended September 30, 2022, compared to $39.5 million for the three months ended September 30, 2021.
+Added: The $23.1 million decrease was attributable to a decrease of $11.7 million in research and development GMP manufacturing and other raw material purchases.
+Added: Additionally, we incurred $6.7 million less expense in third-party research and development consulting fees, primarily related to non-clinical GLP toxicology studies, and a decrease of $4.7 million in employee compensation expenses.
General and Administrative Expenses
−Removed: General and administrative expenses were $9.9 million for the three months ended June 30, 2022, compared to $10.1 million for the three months ended June 30, 2021.
−Removed: The decrease of approximately $0.2 million was primarily attributable to a decrease of $1.1 million in professional fees related to market research, recruiting, accounting, and patient advocacy activities.
−Removed: This was partially offset by $0.9 million of incremental employee compensation expenses.
+Added: General and administrative expenses were $8.7 million for the three months ended September 30, 2022, compared to $11.2 million for the three months ended September 30, 2021.
+Added: The decrease of approximately $2.5 million was primarily attributable to a decrease of $1.3 million in professional fees related to pre-commercialization, recruiting and patient advocacy activities.
+Added: Additionally, we incurred $1.2 million less in employee compensation expenses.
Other Income (Expense)
Interest Expense
−Removed: Interest expense was $0.9 million for the three months ended June 30, 2022, compared to $0.2 million for the three months ended June 30, 2021.
+Added: Interest expense was $1.2 million for the three months ended September 30, 2022, compared to $0.5 million for the three months ended September 30, 2021.
The increase of approximately $0.7 million was primarily attributable to interest expense incurred under the Term Loan Agreement which we entered into in the third quarter of 2021.
−Removed: Results of Operations for the Six Months ended June 30, 2022 and 2021
−Removed: The following table summarizes our results of operations for the six months ended June 30, 2022 and 2021 (in thousands):
−Removed: For the Six Months
−Removed: Ended June 30,
+Added: Results of Operations for the Nine Months ended September 30, 2022 and 2021
+Added: The following table summarizes our results of operations for the nine months ended September 30, 2022 and 2021 (in thousands):
+Added: For the Nine Months
+Added: Ended September 30,
Operating expenses:
9 unchanged sentences
Research and Development Expenses
−Removed: Research and development expenses were $60.9 million for the six months ended June 30, 2022, compared to $54.5 million for the six months ended June 30, 2021.
−Removed: The $6.4 million increase was primarily attributable to an increase of $8.9 million in employee compensation, which included $2.2 million of one-time severance and termination costs in connection with the reduction in force announced in March 2022.
−Removed: We also incurred an increase of $2.6 million of clinical study CRO activities and consulting for regulatory and clinical studies.
−Removed: This was partially offset by a year-over-year decrease of $5.1 million in research and development licensing fees and manufacturing expenses.
+Added: Research and development expenses were $77.3 million for the nine months ended September 30, 2022, compared to $94.0 million for the nine months ended September 30, 2021.
+Added: The $16.7 million decrease was primarily attributable to a decrease of $12.0 million in research and development GMP manufacturing and other raw material purchases.
+Added: We also incurred a year-over-year decrease of $6.0 million in research and development licensing fees and $2.9 million less expenses in third-party research and development consulting fees, mainly related to GLP toxicology studies.
+Added: This was partially offset by an increase of $4.2 million in employee compensation, which included $2.2 million of severance and one-time termination costs in connection with the reprioritization of programs announced in March 2022.
General and Administrative Expenses
−Removed: General and administrative expenses were $21.3 million for the six months ended June 30, 2022, compared to $18.4 million for the six months ended June 30, 2021.
−Removed: The increase of approximately $2.9 million was primarily attributable to $3.7 million of incremental employee compensation expenses, which included $0.4 million of one-time severance and termination costs and $1.2 million of non-cash stock-based compensation.
−Removed: This was partially offset by a year-over-year decrease of $0.8 million in professional fees related to insurance, legal, recruiting and patient advocacy activities.
+Added: General and administrative expenses were $30.0 million for the nine months ended September 30, 2022, compared to $29.5 million for the nine months ended September 30, 2021.
+Added: The increase of approximately $0.5 million was primarily attributable to $2.6 million of incremental compensation expense, which included $0.4 million of severance and one-time termination costs and $0.9 million of non-cash stock-based compensation.
+Added: This was partially offset with a year-over-year decrease of $2.1 million in professional fees mainly related to lower recruiting and patient advocacy activities.
Other Income (Expense)
Interest Expense
−Removed: Interest expense was $1.8 million for the six months ended June 30, 2022, compared to $0.2 million for the six months ended June 30, 2021.
+Added: Interest expenses were $3.0 million for the nine months ended September 30, 2022, compared to $0.7 million for the nine months ended September 30, 2021.
The increase of approximately $2.3 million was primarily attributable to interest expense incurred under the Term Loan Agreement which we entered into in the third quarter of 2021.
Interest Income
−Removed: Interest income for the six months ended June 30, 2022 and 2021 primarily consisted of interest earned on our savings account.
+Added: Interest income for the nine months ended September 30, 2022 and 2021 primarily consisted of interest earned on our savings account.
Liquidity and Capital Resources
Since our inception, we have not generated any revenue and have incurred significant operating losses.
−Removed: As of June 30, 2022, we had cash and cash equivalents of $66.2 million.
−Removed: From inception through June 30, 2022, we have funded our operations primarily through equity financings, raising an aggregate of $319.0 million in gross proceeds from our initial public offering and private placements of convertible preferred stock as well as sales of common stock pursuant to our Sales Agreement.
−Removed: Specifically, between March and July 2020, we closed on the sale of an aggregate of 10,000,000 shares of Series A convertible preferred stock for gross proceeds of $30.0 million.
−Removed: In July and August 2020, we closed on the sale of an aggregate of 5,647,048 shares of Series B convertible
−Removed: preferred stock for gross proceeds of $96.0 million.
+Added: As of September 30, 2022, we had cash and cash equivalents of $34.3 million.
+Added: From inception through September 30, 2022, we have funded our operations primarily through equity financings, raising an aggregate of $319.0 million in gross proceeds from our initial public offering and private placements of convertible preferred stock as well as sales of common stock pursuant to our Sales Agreement (as defined below).
+Added: Specifically, between March and July 2020, we closed on the sale of an aggregate of 10,000,000 shares of Series A
+Added: convertible preferred stock for gross proceeds of $30.0 million.
+Added: In July and August 2020, we closed on the sale of an aggregate of 5,647,048 shares of Series B convertible preferred stock for gross proceeds of $96.0 million.
In September 2020, we raised gross proceeds of $181.0 million in our initial public offering.
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We drew $30.0 million in term loans on the Closing Date and an additional $10.0 million in term loans on December 29, 2021.
+Added: We did not draw the additional $20.0 million tranche prior to its expiration in September 30, 202.
The loan repayment schedule provides for interest only payments until August 31, 2024, followed by consecutive monthly payments of principal and interest.
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In April 2022, we sold 2,000,000 shares of common stock pursuant to the Sales Agreement and received net proceeds of $11.6 million.
−Removed: No other shares of common stock have been issued and sold pursuant to the Sales Agreement as of June 30, 2022.
+Added: No other shares of common stock have been issued and sold pursuant to the Sales Agreement as of September 30, 2022.
+Added: On October 21, 2022, we entered into a securities purchase agreement, or the Securities Purchase Agreement, with Audentes Therapeutics, Inc.
+Added: (d/b/a Astellas Gene Therapy), or Astellas, pursuant to which we agreed to issue and sell to Astellas in a private placement an aggregate of 7,266,342 shares of common stock for aggregate gross proceeds of $30.0 million.
+Added: The Private Placement closed on October 24, 2022.
+Added: Also on October 21, 2022 we entered into a registration rights agreement pursuant to which we agreed to register the resale of the shares purchased under the Securities Purchase Agreement no later than April 24, 2023.
+Added: On October 21, 2022, we entered into an option agreement, or the Option Agreement, with Astellas, granting Astellas an exclusive option to obtain exclusive, worldwide, royalty and milestone-bearing rights and licenses related to TSHA-120 and TSHA-102.
+Added: As partial consideration for the rights granted to Astellas under the Option Agreement, Astellas will pay us a one-time payment in the amount of $20.0 million, or the Upfront Payment, within 30 days after receipt of an invoice for such payment (see Note 12 to the unaudited condensed consolidated financial statements located in “Part I – Financial Information, Item 1.
+Added: Financial Statements” in this Quarterly Report on Form 10-Q).
+Added: The invoice for the Upfront Payment was sent to Astellas on October 24, 2022.
+Added: In October 2022, we entered into an Underwriting Agreement with Goldman Sachs & Co.
+Added: LLC, or the Underwriter, to issue and sell 14,000,000 shares of our common stock, par value $0.0001 per share, in an underwritten public offering, or the Offering, pursuant to effective registration statement on Form S-3 and a related prospectus and prospectus supplement.
+Added: The offering price to the public was $2.00 per share and the Underwriter purchased the shares from the us pursuant to the Underwriting Agreement at a price of $1.88 per share.
+Added: In addition, we granted the Underwriter an option to purchase, for a period of 30 days, up to an additional 2,100,000 shares of our common stock.
+Added: The Offering closed on October 31, 2022 and we received net proceeds of $25.6 million after deducting underwriting discounts, commissions and estimated offering expenses.
+Added: The Company estimates that the net proceeds from the Offering will be approximately $29.6 million if the Underwriter exercises in full its option to purchase additional shares of the Company’s common stock after deducting underwriting discounts and commissions and estimated offering expenses (see Note 12 to the unaudited condensed consolidated financial statements located in “Part I – Financial Information, Item 1.
+Added: Financial Statements” in this Quarterly Report on Form 10-Q).
Funding Requirements
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If we fail to complete the development of our product candidates in a timely manner or fail to obtain their regulatory approval, our ability to generate future revenue will be compromised.
−Removed: We do not know when, or if, we will generate any revenue from our product candidates, and we do not expect to generate significant revenue unless and until we obtain regulatory approval of, and commercialize, our product candidates.
+Added: We do not know when, or if, we will generate any revenue from our product candidates, and we do not expect to generate significant revenue unless
+Added: and until we obtain regulatory approval of, and commercialize, our product candidates.
We expect our expenses to decrease in connection with our ongoing activities largely due to the strategic reprioritization of product candidates and the reduction in force announced in March 2022.
−Removed: We will continue the research and development of, initiate clinical trials of and seek marketing approval for specific product candidates, as well as continue the build out of our cGMP manufacturing facility in Durham, North Carolina.
+Added: W e will continue the research and development of, initiate clinical trials of and seek marketing approval for specific product candidates .
In addition, if we obtain approval for any of our product candidates, we then expect to incur significant commercialization expenses related to sales, marketing, manufacturing and distribution.
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If we are unable to raise capital when needed or on attractive terms, we could be forced to delay, reduce or eliminate our research and development programs or future commercialization efforts.
−Removed: As of June 30, 2022, our material cash requirements consisted of $49.9 million in total lease payments entered into since inception.
−Removed: Our most significant purchase commitments consist of approximately $6.0 million related to the build-out of our cGMP manufacturing facility and $4.0 million in cancellable purchase obligations to our CROs.
−Removed: We believe that our existing cash and cash equivalents, along with full access to the term loan facility will enable us to fund our operating expenses and capital requirements into the fourth quarter of 2023.
−Removed: This estimate reflects our strategic prioritization efforts to improve operating efficiency previously announced in March 2022.
+Added: We believe that our existing cash and cash equivalents, along with the $50.0 million payment from Astellas and the anticipated $25.6 million net proceeds received from the Offering, will enable us to fund our operating expenses and capital requirements into the first quarter of 2024.
We will require additional capital to fund the research and development of our product candidates, to fund our manufacturing activities, to fund precommercial activities of our programs and for working capital and general corporate purposes.
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the scope, progress, costs and results of discovery, preclinical development, laboratory testing and clinical trials for TSHA-102, TSHA-105, TSHA-118, TSHA-120, TSHA-121 and any current and future product candidates that we advance;
−Removed: our ability to access sufficient additional capital on a timely basis and on favorable terms, including with respect to our term loan facility with Silicon Valley Bank;
+Added: our ability to access sufficient additional capital on a timely basis and on favorable terms;
the extent to which we develop, in-license or acquire other product candidates and technologies in our gene therapy product candidate pipeline;
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the revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval;
+Added: whether we access the remaining tranches under our term loan facility with Silicon Valley Bank;
the costs of operating as a public company.
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Any future additional debt financing and equity financing, if available, may involve agreements that include covenants limiting and restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures, entering into profit-sharing or other arrangements or declaring dividends.
−Removed: If we raise additional funds through collaborations, strategic alliances or marketing, distribution or licensing arrangements with third parties, we may be required to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or to grant licenses on terms that may not be favorable to us.
+Added: If we raise additional funds through collaborations, strategic alliances or marketing, distribution or licensing
+Added: arrangements with third parties, we may be required to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or to grant licenses on terms that may not be favorable to us.
We are continuing to assess the effect that the COVID-19 pandemic may have on our business and operations.
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Further, disruption of global financial markets and a recession or market correction, including as a result of the COVID-19 pandemic, the ongoing military conflict between Russia and Ukraine and the related sanctions imposed against Russia, and other global macroeconomic factors such as inflation, could reduce our ability to access capital, which could in the future negatively affect our liquidity and the value of our common stock.
−Removed: The following table shows a summary of our cash flows for the six months ended June 30, 2022 and 2021 (in thousands):
−Removed: For the Six Months Ended June 30,
+Added: The following table shows a summary of our cash flows for the nine months ended September 30, 2022 and 2021 (in thousands):
+Added: For the Nine Months Ended September 30,
Net cash used in operating activities
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Operating Activities
−Removed: For the six months ended June 30, 2022, our net cash used in operating activities of $74.0 million primarily consisted of a net loss of $84.0 million, primarily attributable to our spending on research and development expenses.
−Removed: The net loss of $84.0 million was partially offset by adjustments for non-cash items, primarily stock-based compensation and depreciation expense of $10.0 million.
−Removed: For the six months ended June 30, 2021, our net cash used in operating activities of $44.9 million primarily consisted of a net loss of $73.0 million, primarily attributable to our spending on research and development expenses.
−Removed: The net loss of $73.0 million was partially offset by adjustments for non-cash items, primarily the up-front license fee of $5.5 million to HHF related to the acquisition of TSHA-120 and stock-based compensation of $8.1 million.
−Removed: The $73.0 million net loss was also partially offset by a $14.1 million source of cash provided by operating assets and liabilities, primarily resulting from an increase in accounts payable and accrued expenses.
+Added: For the nine months ended September 30, 2022, our net cash used in operating activities of $102.7 million primarily consisted of a net loss of $110.3 million, primarily attributable to our spending on research and development expenses.
+Added: The net loss of $110.3 million was partially offset by adjustments for non-cash items, primarily stock-based compensation, research and development license fees and depreciation expense of $16.6 million.
+Added: Additional cash used in operating activities of $9.0 million was primarily due to a decrease in accounts payable and accrued expenses.
+Added: For the nine months ended September 30, 2021, our net cash used in operating activities of $76.8 million primarily consisted of a net loss of $124.1 million, primarily attributable to our spending on research and development expenses.
+Added: The net loss of $124.1 million was partially offset by adjustments for non-cash items, primarily stock-based compensation of $13.2 million, and the add back of the up-front license fee of $5.5 million paid to HHF related to the acquisition of TSHA-120 which is treated as an investing outflow as well as other license fees of $1.3 million.
+Added: The $124.1 million net loss was also partially offset by a $26.6 million increase in the cash provided by operating assets and liabilities, primarily resulting from an increase in accounts payable and accrued expenses.
Investing Activities
−Removed: During the six months ended June 30, 2022, investing activities used $19.5 million of cash primarily attributable to the regulatory milestone payment of $3.0 million paid to Abeona pursuant to the CLN1 Agreement, and $16.3 million in capital expenditures related to our in-house manufacturing facility.
−Removed: During the six months ended June 30, 2021, investing activities used $9.0 million of cash attributable to the up front license fee payment of $5.5 million to acquire exclusive worldwide rights to TSHA-120, for the treatment of GAN, and $3.5 million in capital expenditures related to our in-house manufacturing facility and office space.
+Added: During the nine months ended September 30, 2022, investing activities used $22.6 million of cash primarily attributable to research and development license payments of $4.3 million, including regulatory milestone payments paid to Abeona pursuant to the Rett and CLN1 Agreements and $18.3 million in capital expenditures related to our in-house manufacturing facility and research and development lab.
+Added: During the nine months ended September 30, 2021, investing activities used $13.0 million of cash primarily attributable to the upfront license fee payment of $5.5 million to acquire exclusive worldwide rights to TSHA-120, for the treatment of GAN, and capital expenditures related to our in-house manufacturing facility and office space.
Financing Activities
−Removed: During the six months ended June 30, 2022, financing activities provided $10.7 million of cash, which is primarily attributable to $11.6 million net proceeds from the sale of 2,000,000 shares of common stock pursuant to the Sales Agreement and $0.3 million of ESPP contributions.
−Removed: The proceeds were partially offset by the payment of shelf registration costs, and other financing transactions.
−Removed: No financing activities took place during the six months ended June 30, 2021.
+Added: During the nine months ended September 30, 2022, financing activities provided $10.4 million of cash, which is primarily attributable to $11.6 million net proceeds from the sale of 2,000,000 shares of common stock pursuant to the Sales Agreement and $0.3 million of ESPP contributions.
+Added: The proceeds were partially offset by the payment of shelf registration costs, and other financing
+Added: transactions .
+Added: During the nine months ended September 30, 2021, financing activities provided $30.0 million of cash, which is attributable to the receipt of $30.0 million net proceeds from our Term Loan with Silicon Valley Bank.
Off-Balance Sheet Arrangements
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In April 2012, the Jumpstart Our Business Startups Act of 2012, or JOBS Act, was enacted.
−Removed: Section 107 of the JOBS Act provides that an “emerging growth company” can take advantage of the extended transition period provided in Section 7(a)(2)(B) of
−Removed: the Securities Act of 1933, as amended, for complying with new or revised accounting standards.
+Added: Section 107 of the JOBS Act provides that an “emerging growth company” can take advantage of the extended transition period provided in Section 7(a)(2)(B) of the Securities Act of 1933, as amended, for complying with new or revised accounting standards.
Thus, an emerging growth company can delay the adoption of certain accounting standards until those standards would otherwise apply to private companies.
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We may continue to be a smaller reporting company if either (i) the market value of our shares held by non-affiliates is less than $250 million or (ii) our annual revenue was less than $100 million during the most recently completed fiscal year and the market value of our shares held by non-affiliates is less than $700 million.
−Removed: If we are a smaller reporting company at the time we cease to be an emerging growth company, we may continue to rely on exemptions from certain disclosure requirements that are available to smaller reporting companies.
+Added: If we are a smaller reporting company at the time we cease to be an emerging growth company, we may continue to rely on exemptions from certain disclosure requirements that are available to smaller reporting
Specifically, as a smaller reporting company, we may choose to present only the two most recent fiscal years of audited financial statements in our Annual Report on Form 10-K and, similar to emerging growth companies, smaller reporting companies have reduced disclosure obligations regarding executive compensation.
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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.