Genprex Inc

Previous wording

The TUSC2 gene, which is the key component of REQORSA and plays a vital role in cancer suppression and normal cell metabolism, is one of a series of genes on the short arm of Chromosome 3 whose therapeutic use is covered by our exclusive worldwide licenses from The University of Texas MD Anderson Cancer Center (“MD Anderson”). We believe that our ONCOPREX Delivery System allows for the delivery of a number of cancer-fighting tumor suppressor genes, alone or in combination with other cancer therapies, to combat multiple types of cancer and we are in early stages of discovery programs to identify other cancer candidates. In August 2022, we entered into a three-year sponsored research agreement with MD Anderson to support further preclinical studies of TUSC2 and other tumor suppressor genes. Additionally, we are collaborating with MD Anderson to discover, develop and utilize biomarkers to (i) select the patient population most likely to respond to REQORSA; (ii) predict and measure target engagement; and (iii) enable decisions on progression of our drug candidates to the next phase of development. MD Anderson is currently analyzing biomarkers that would indicate lack of response in lung cancer that could enrich our population of responders in our clinical trials and enhance patient screening and enrollment in order to increase the likelihood of potential success of the Acclaim studies for the Company.

Current wording

The TUSC2 gene, which is the key component of REQORSA and plays a vital role in cancer suppression and normal cell metabolism, is one of a series of genes on the short arm of Chromosome 3 whose therapeutic use is covered by our exclusive worldwide licenses from The University of Texas MD Anderson Cancer Center (“MD Anderson”). We believe that our ONCOPREX Delivery System allows for the delivery of a number of cancer-fighting tumor suppressor genes, alone or in combination with other cancer therapies, to combat multiple types of cancer and we are in early stages of discovery programs to identify other cancer candidates. In August 2022, we entered into a three-year sponsored research agreement with MD Anderson to support further preclinical studies of TUSC2 and other tumor suppressor genes. Additionally, we are collaborating with MD Anderson to discover, develop and utilize biomarkers to select the patient population most likely to respond to REQORSA and enable decisions on progression of our drug candidates to the next phase of development. MD Anderson is currently analyzing biomarkers that would indicate lack of response in lung cancer that could enrich our population of responders in our clinical trials and enhance patient screening and enrollment in order to increase the likelihood of potential success of the Acclaim studies for the Company.

Previous wording

Acclaim-3: We are currently enrolling and treating patients in the Phase 1 dose escalation portion of our Phase 1/2 Acclaim-3 clinical trial. The Acclaim-3 clinical trial uses a combination of REQORSA and Genentech, Inc.’s Tecentriq® (atezolizumab) as maintenance therapy in patients with extensive stage small cell lung cancer (“ES-SCLC”) who did not develop tumor progression after receiving Tecentriq and chemotherapy as initial standard treatment. Patients are treated with REQORSA and Tecentriq until disease progression or unacceptable toxicity is experienced. In January 2024, we opened the Phase 1 portion of the Acclaim-3 study for enrollment and enrolled and dosed the first patient in May 2024. We expect to complete the Phase 1 dose escalation portion of the study during the second half of 2024 and we expect to start the Phase 2 expansion portion of our Acclaim-3 study in the second half of 2024. The first patient treated in the Phase 1 dose escalation portion of the Acclaim-3 trial experienced an initial positive response after enrollment and dosing commenced in May. The patient had a partial remission (“PR”), which is defined as at least a thirty percent (30%) decrease in tumor size, from the time the patient had a baseline CT scan after induction therapy and prior to the start of maintenance therapy to the time of the CT scan performed after two cycles of maintenance therapy. As the maintenance therapy consists of REQORSA and Tecentriq, and the patient had already received four cycles of Tecentriq during induction therapy and thus responses to Tecentriq would likely have occurred earlier, we believe this suggests that REQORSA may be providing clinical benefit. A recent CT scan, performed after four cycles of maintenance therapy (three months), confirms that the patient had a 30% decrease in tumor size in measurable lesions; however, one lesion not previously measurable had grown in size, thus leading to a conclusion of disease progression at three months. In June 2023, the United States Food and Drug Administration (“FDA”) granted Fast Track Designation for the Acclaim-3 treatment combination of REQORSA and Tecentriq as maintenance therapy in patients with ES-SCLC who did not develop tumor progression after receiving Tecentriq and chemotherapy as initial standard treatment. In August 2023, the FDA granted Orphan Drug Designation to REQORSA for the treatment of SCLC.

Current wording

Acclaim-3: We are currently enrolling and treating patients in the Phase 1 dose escalation portion of our Phase 1/2 Acclaim-3 clinical trial. The Acclaim-3 clinical trial uses a combination of REQORSA and Genentech, Inc.’s Tecentriq® (atezolizumab) as maintenance therapy in patients with extensive stage small cell lung cancer (“ES-SCLC”) who did not develop tumor progression after receiving Tecentriq and chemotherapy as initial standard treatment. Patients are treated with REQORSA and Tecentriq until disease progression or unacceptable toxicity is experienced. In January 2024, we opened the Phase 1 portion of the Acclaim-3 study for enrollment and enrolled and dosed the first patient in May 2024. In October 2024, the Company announced the completion of the 0.09 mg/kg dose group of the Phase 1 portion and that there were no dose limiting toxicities in this dose group. The Acclaim-3 Safety Review Committee therefore approved escalation to the highest dose group of 0.12 mg/kg, which will now be enrolled. We continue to anticipate completion of enrollment in the Phase 1 dose escalation portion of the study and to start the Phase 2 expansion portion of the study in the second half of 2024, dependent on the number of patients needed to be enrolled in the 0.12 mg/kg dose group. The first patient treated in the Phase 1 dose escalation portion of the Acclaim-3 trial experienced an initial positive response after enrollment and dosing commenced in May. The patient had a partial remission (“PR”), which is defined as at least a thirty percent (30%) decrease in tumor size, from the time the patient had a baseline CT scan after induction therapy and prior to the start of maintenance therapy to the time of the CT scan performed after two cycles of maintenance therapy. As the maintenance therapy consists of REQORSA and Tecentriq, and the patient had already received four cycles of Tecentriq during induction therapy and thus responses to Tecentriq would likely have occurred earlier, we believe this suggests that REQORSA may be providing clinical benefit. A follow-up CT scan, performed after four cycles of maintenance therapy (three months), confirmed that the patient still had a 30% decrease in tumor size in measurable lesions; however, one lesion not previously measurable had grown in size, thus leading to a conclusion of disease progression at three months. In June 2023, the United States Food and Drug Administration (“FDA”) granted Fast Track Designation for the Acclaim-3 treatment combination of REQORSA and Tecentriq as maintenance therapy in patients with ES-SCLC who did not develop tumor progression after receiving Tecentriq and chemotherapy as initial standard treatment. In August 2023, the FDA granted Orphan Drug Designation to REQORSA for the treatment of SCLC.

Previous wording

Acclaim-2: The Acclaim-2 trial involved a combination of REQORSA and Merck & Co.’s Keytruda® (pembrolizumab) in patients with late-stage NSCLC whose disease has progressed after treatment with Keytruda. Based on a number of factors, including enrollment challenges and delays due to competition for investigators and eligible patients with numerous other trials involving the same patient population, we have decided to cease enrollment of new patients in the Acclaim-2 trial to prioritize our resources and focus on the other two Acclaim trials in SCLC and NSCLC, respectively. Current patients in the Phase 1 dose escalation portion of the study will continue to be treated until disease progression.

Current wording

Acclaim-2: The Acclaim-2 trial involved a combination of REQORSA and Merck & Co.’s Keytruda® (pembrolizumab) in patients with late-stage NSCLC whose disease has progressed after treatment with Keytruda. As previously announced in August 2024, based on a number of factors, including enrollment challenges and delays due to competition for investigators and eligible patients with numerous other trials involving the same patient population, we decided to cease enrollment of new patients in the Acclaim-2 trial to prioritize our resources and focus on the other two Acclaim trials in SCLC and NSCLC, respectively. The one patient continuing to receive REQORSA treatment in the Phase 1 dose escalation portion of the study will continue to be treated until disease progression.

Previous wording

Acclaim-1: We are currently enrolling and treating patients in the Phase 2a expansion portion of our Phase 1/2 Acclaim-1 clinical trial. The Acclaim-1 trial uses a combination of REQORSA and AstraZeneca’s Tagrisso® (osimertinib) in patients with late-stage NSCLC that has activating epidermal growth factor receptor (“EGFR”) mutations and progression after treatment with Tagrisso. Following the May 2023 completion of the Phase 1 dose escalation portion of the study, the Acclaim-1 Safety Review Committee (“Acclaim-1 SRC”) approved advancement from the Phase 1 dose escalation portion to the Phase 2a expansion portion of the study. Based on a review of safety data which showed no dose limiting toxicities, the Acclaim-1 SRC determined the recommended Phase 2 dose of REQORSA to be 0.12 mg/kg. This was the highest dose level delivered in the Phase 1 portion of the study and is twice the highest dose level delivered in our prior clinical trial combining REQORSA with Tarceva® (erlotinib) for the treatment of late-stage lung cancer. There are still two patients originally enrolled in the Phase 1 dose escalation portion of the study who have had prolonged progression-free survival and continue to receive treatment with REQORSA and Tagrisso, one who attained a PR after the second course of REQORSA and Tagrisso and has maintained this response through 36 courses of treatment (approximately 27 months), and one with stable disease without disease progression through 22 courses of treatment (approximately 16 months) who is also continuing to receive REQORSA and Tagrisso treatment. We opened the Phase 2a expansion portion of the study and enrolled and dosed the first patient in January 2024. The initial trial design of the Phase 2a expansion portion of the study included two cohorts with half being patients who received only prior Tagrisso treatment and the other half being patients who received prior Tagrisso treatment and chemotherapy. However, based on resource prioritization and to focus on the patients for whom REQORSA is most likely to show a benefit, we have decided to limit our enrollment efforts moving forward to patients who received only prior Tagrisso treatment and cease enrollment of the second cohort (patients who received prior Tagrisso treatment and chemotherapy). The Phase 2a expansion portion of the trial with one cohort is now expected to enroll approximately 33 patients. The Phase 2b randomized portion of the study, in which patients progressing on prior Tagrisso treatment will be randomized 1:1 to either REQORSA and Tagrisso combination therapy or to platinum-based chemotherapy, will remain unchanged. There will be an interim analysis following the treatment of 19 patients in the Phase 2a portion of the Acclaim-1 study. We expect to complete the enrollment of the first 19 patients in the Phase 2a expansion portion of the study and conduct an interim analysis in the first half of 2025. The FDA has granted Fast Track Designation for the Acclaim-…

Excerpt shortened here; the source contains the full paragraph.

Current wording

Acclaim-1: We are currently enrolling and treating patients in the Phase 2a expansion portion of our Phase 1/2 Acclaim-1 clinical trial. The Acclaim-1 trial uses a combination of REQORSA and AstraZeneca’s Tagrisso® (osimertinib) in patients with late-stage NSCLC that has activating epidermal growth factor receptor (“EGFR”) mutations and progression after treatment with Tagrisso. Following the May 2023 completion of the Phase 1 dose escalation portion of the study, the Acclaim-1 Safety Review Committee (“Acclaim-1 SRC”) approved advancement from the Phase 1 dose escalation portion to the Phase 2a expansion portion of the study. Based on a review of safety data which showed no dose limiting toxicities, the Acclaim-1 SRC determined the recommended Phase 2 dose of REQORSA to be 0.12 mg/kg. This was the highest dose level delivered in the Phase 1 portion of the study and is twice the highest dose level delivered in our prior clinical trial combining REQORSA with Tarceva® (erlotinib) for the treatment of late-stage lung cancer. There are still two patients originally enrolled in the Phase 1 dose escalation portion of the study who have had prolonged progression-free survival and continue to receive treatment with REQORSA and Tagrisso, one who attained a PR after the second course of REQORSA and Tagrisso and has maintained this response through 41 courses of treatment (approximately 30 months), and one with stable disease without disease progression through 26 courses of treatment (approximately 19 months) who is also continuing to receive REQORSA and Tagrisso treatment. We opened the Phase 2a expansion portion of the study and enrolled and dosed the first patient in January 2024. The initial trial design of the Phase 2a expansion portion of the study included two cohorts with half being patients who received only prior Tagrisso treatment and the other half being patients who received prior Tagrisso treatment and chemotherapy. However, as previously announced in August 2024, based on resource prioritization and to focus on the patients for whom REQORSA is most likely to show a benefit, we decided to limit our enrollment efforts moving forward to patients who received only prior Tagrisso treatment and cease enrollment of the second cohort (patients who received prior Tagrisso treatment and chemotherapy). The Phase 2a expansion portion of the trial with one cohort is now expected to enroll approximately 33 patients. The Phase 2b randomized portion of the study, in which patients progressing on prior Tagrisso treatment will be randomized 1:1 to either REQORSA and Tagrisso combination therapy or to platinum-based chemotherapy, will remain unchanged. There will be an interim analysis following the treatment of 19 patients in the Phase 2a portion of the Acclaim-1 study. We expect to complete the enrollment of the first 19 patients in the Phase 2a expansion portion of the study and conduct an interim analysis in the first half of 2025. The FDA has granted Fast…

Excerpt shortened here; the source contains the full paragraph.

Previous wording

In diabetes, we have exclusively licensed from the University of Pittsburgh of the Commonwealth System of Higher Education (“University of Pittsburgh”) multiple technologies relating to the development of a gene therapy product for each of Type 1 and Type 2 diabetes. The same general novel approach is used in each of Type 1 and Type 2 diabetes whereby an adeno-associated virus (“AAV”) vector containing the Pdx1 and MafA genes is administered directly into the pancreatic duct. In humans, this can be done with a routine endoscopy procedure. Our diabetes product candidates are currently being evaluated and optimized in preclinical studies at the University of Pittsburgh. GPX-002 is being developed using the same construct for the treatment of both Type 1 diabetes and Type 2 diabetes. GPX-002 for Type 1 diabetes is designed to work by transforming alpha cells in the pancreas into functional beta-like cells, which can produce insulin but may be distinct enough from beta cells to evade the body’s immune system. In a similar approach, GPX-002 for Type 2 diabetes (formerly known as GPX-003), where autoimmunity is not at play, is believed to work by replenishing and rejuvenating exhausted beta cells that make insulin. We finalized the components of the diabetes construct to take forward for nonclinical studies and in December 2023, we submitted a request to meet with the FDA to obtain their guidance on the nonclinical studies needed to file an Investigational New Drug (“IND”) application and initiate first-in-human studies. As a result of the FDA’s response, we will continue with our planned additional nonclinical studies before requesting regulatory guidance for the IND-enabling studies. We are currently working with the University of Pittsburgh on species analyses for the animal models as well as on other regulatory and clinical strategic planning and anticipate requesting further regulatory guidance from the FDA in the first half of 2025. In October 2023, we entered into a one-year extension to our August 2022 sponsored research agreement with the University of Pittsburgh for the use of GPX-002 in a non-human primate (“NHP”) model in Type 2 diabetes. The extension includes a revised research plan to encompass our most recent technologies to which we acquired exclusive rights from the University of Pittsburgh in July 2023. These include using a MafB promoter to drive expression of the Pdx1 and MafA transcription factors that can potentially be used for both Type 1 and Type 2 diabetes. See also “Note 7 – Commitments and Contingencies” to our unaudited condensed financial statements included in this Quarterly Report on Form 10-Q.

Current wording

In diabetes, we have exclusively licensed from the University of Pittsburgh of the Commonwealth System of Higher Education (“University of Pittsburgh”) multiple technologies relating to the development of a gene therapy product for each of Type 1 and Type 2 diabetes. The same general novel approach is used in each of Type 1 and Type 2 diabetes whereby an adeno-associated virus (“AAV”) vector containing the Pdx1 and MafA genes is administered directly into the pancreatic duct. In humans, this can be done with a routine endoscopy procedure. Our diabetes product candidates are currently being evaluated and optimized in preclinical studies at the University of Pittsburgh. GPX-002 is being developed using the same construct for the treatment of both Type 1 diabetes and Type 2 diabetes. GPX-002 for Type 1 diabetes is designed to work by transforming alpha cells in the pancreas into functional beta-like cells, which can produce insulin but may be distinct enough from beta cells to evade the body’s immune system. In a similar approach, GPX-002 for Type 2 diabetes (formerly known as GPX-003), where autoimmunity is not at play, is believed to work by replenishing and rejuvenating exhausted beta cells that make insulin. We finalized the components of the diabetes construct to take forward for nonclinical studies and in December 2023, we submitted a request to meet with the FDA to obtain their guidance on the nonclinical studies needed to file an Investigational New Drug (“IND”) application and initiate first-in-human studies. As a result of the FDA’s response, we will continue with our planned additional nonclinical studies before requesting regulatory guidance for the IND-enabling studies. We are currently working with the University of Pittsburgh on species analyses for the animal models as well as on other regulatory and clinical strategic planning and anticipate requesting further regulatory guidance from the FDA in the first half of 2025. In October 2023, we entered into a one-year extension to our August 2022 sponsored research agreement with the University of Pittsburgh for the use of GPX-002 in a non-human primate (“NHP”) model in Type 2 diabetes. The extension includes a revised research plan to encompass our most recent technologies to which we acquired exclusive rights from the University of Pittsburgh in July 2023. These include using a MafB promoter to drive expression of the Pdx1 and MafA transcription factors that can potentially be used for both Type 1 and Type 2 diabetes. Additionally, in September 2024, we announced that we are considering various strategic alternatives and opportunities to enhance stockholder value, including evaluating ways to optimize our clinical and research programs and operational strategies, such as our intention to potentially transfer our diabetes clinical development program and our diabetes gene therapy assets into a new, initially wholly-owned subsidiary (“NewCo”). NewCo would focus on developing and commercia…

Excerpt shortened here; the source contains the full paragraph.

Previous wording

We believe that the following accounting policies are the most critical to aid in fully understanding and evaluating our reported financial results, and they require our most difficult, subjective or complex judgments, resulting from the need to make estimates about the effect of matters that are inherently uncertain**.**

Current wording

We believe that the following accounting policies and estimates are the most critical to aid in fully understanding and evaluating our reported financial results, and they require our most difficult, subjective or complex judgments, resulting from the need to make estimates about the effect of matters that are inherently uncertain**.**

Previous wording

We expect our research and development expenses to increase in the future as we (i) advance our current and future product candidates into and through clinical trials, (ii) transition some of our manufacturing activities to new vendors for a variety of reasons, such as to incorporate more advanced processes and scale production, including any additional work that has been or may be required to successfully adapt our process to these new processes, (iii) pursue regulatory approval of our current and potential product candidates in the U.S. and Europe, and (iv) expand our research programs to include new therapies and new therapy combinations. The process of conducting the necessary pre-clinical and clinical research to obtain regulatory approval is costly and time-consuming. The actual probability of success for our current and potential product candidates may be affected by a variety of factors including the quality of our current and potential product candidates, early clinical data, investment in our clinical program, competition, manufacturing capability and commercial viability, and limited contracted partners. We may never succeed in achieving regulatory approval for any of our current or future product candidates. As a result of the uncertainties discussed above, we are unable to determine the duration and completion costs of our research and development projects or when and to what extent we will generate revenue from the commercialization and sale of our product candidates, if at all. However, we continue to evaluate ways to optimize our clinical and research programs and operational strategies, as part of our ongoing prioritization initiative.

Current wording

We expect our research and development expenses to increase in the future as we (i) advance our current and future product candidates into and through clinical trials, (ii) transition some of our manufacturing activities to new vendors for a variety of reasons, such as to incorporate more advanced processes and scale production, including any additional work that has been or may be required to successfully adapt our process to these new processes, (iii) pursue regulatory approval of our current and potential product candidates in the U.S. and Europe, and (iv) expand our research programs to include new therapies and new therapy combinations. The process of conducting the necessary pre-clinical and clinical research to obtain regulatory approval is costly and time-consuming. The actual probability of success for our current and potential product candidates may be affected by a variety of factors including the quality of our current and potential product candidates, early clinical data, investment in our clinical program, competition, manufacturing capability and commercial viability, and limited contracted partners. We may never succeed in achieving regulatory approval for any of our current or future product candidates. As a result of the uncertainties discussed above, we are unable to determine the duration and completion costs of our research and development projects or when and to what extent we will generate revenue from the commercialization and sale of our product candidates, if at all. However, we continue to evaluate ways to optimize our clinical and research programs and operational strategies, as part of our ongoing prioritization initiative. Additionally, we are considering various strategic alternatives and opportunities to enhance stockholder value.

Previous wording

Comparison of the Three and Six Months Ended June 30, 2024, and 2023

Current wording

Comparison of the Three and Nine Months Ended September 30, 2024, and 2023

Previous wording

The following summarizes our results of operations for the three and six months ended June 30, 2024, and 2023.

Current wording

The following summarizes our results of operations for the three and nine months ended September 30, 2024 and 2023.

Previous wording

Research and Development (“R&D”) expense for the three months ended June 30, 2024 was $1,666,522, compared to $3,976,917 for the three months ended June 30, 2023, a decrease of $2,310,395, or 58%. This decrease was primarily due to (i) changes in CDMOs that significantly reduced manufacturing expense, and (ii) implementation of expense reduction strategies by leadership in the three months ended June 30, 2024, which reduced travel expenses and reduced headcount and associated overheads of R&D staff from 18 employees at June 30, 2023 to 13 employees at June 30, 2024. Additionally, the Company incurred a higher than normal manufacturing expense in the three months ended June 30, 2023 due to the Company switching CDMOs that required both comparability and scaling of programs and accordingly resulted in added costs incurred during the second quarter of 2023 as compared to the three months ended June 30, 2024.

Current wording

Research and Development (“R&D”) expense for the three months ended September 30, 2024 was $2,756,081, compared to $4,616,546 for the three months ended September 30, 2023, a decrease of $1,860,465, or 40%. This decrease was primarily due to (i) changes in CDMOs that significantly reduced manufacturing and R&D materials expense, and (ii) implementation of expense reduction strategies by leadership in the three months ended September 30, 2024, which reduced travel expenses and reduced headcount and associated overhead of R&D staff from 18 employees at September 30, 2023 to 13 employees at September 30, 2024.

Previous wording

Research and Development (“R&D”) expense for the six months ended June 30, 2024 was $4,940,902, compared to $9,287,065 for the six months ended June 30, 2023, a decrease of $4,346,163, or 47%. This decrease was primarily due to (i) changes in CDMOs that significantly reduced manufacturing expense, (ii) a significant reduction in share-based compensation for R&D personnel due to the timing of equity awards, and (iii) implementation of expense reduction strategies by leadership in the six months ended June 30, 2024, which reduced travel expenses and reduced headcount and associated overheads of R&D staff from 18 employees at June 30, 2023 to 13 employees at June 30, 2024. Additionally, the Company had a higher than normal manufacturing expense in the six months ended June 30, 2023 due to the Company switching CDMOs that required both comparability and scaling of programs accordingly compared to the six months ended June 30, 2024.

Current wording

Research and Development (“R&D”) expense for the nine months ended September 30, 2024 was $7,696,982, compared to $13,903,611 for the nine months ended September 30, 2023, a decrease of $6,206,629, or 45%. This decrease was primarily due to (i) changes in CDMOs that significantly reduced manufacturing expense, (ii) a significant reduction in share-based compensation for R&D personnel due to the timing of equity awards, and (iii) implementation of expense reduction strategies by leadership in the nine months ended September 30, 2024, which reduced travel expenses and reduced headcount and associated overhead of R&D staff from 18 employees at September 30, 2023 to 13 employees at September 30, 2024. Additionally, the Company had a higher than normal manufacturing expense in the nine months ended September 30, 2023 due to the Company switching CDMOs that required both comparability and scaling of programs accordingly compared to the nine months ended September 30, 2024.

Previous wording

General and administrative (“G&A”) expense for the six months ended June 30, 2024 was $7,569,140, compared to $8,007,587 for the six months ended June 30, 2023, a decrease of $438,447, or 5%. This decrease was primarily due to the implementation of expense reduction strategies by leadership in the six months ended June 30, 2024, which reduced travel expenses, the number of professional service providers and associated expenses, and reduced headcount and associated overheads of G&A staff from 12 employees at June 30, 2023 to 8 employees at June 30, 2024.

Current wording

General and administrative (“G&A”) expense for the three months ended September 30, 2024 was $1,566,085, compared to $3,166,057 for the three months ended September 30, 2023, a decrease of $1,599,972, or 51%. This decrease was primarily due to the implementation of expense reduction strategies by leadership in the nine months ended September 30, 2024, which significantly reduced travel expenses, the number of professional service providers and associated expenses, and reduced headcount and associated overhead of G&A staff from 13 employees at September 30, 2023 to 7 employees at September 30, 2024.

Previous wording

General and administrative (“G&A”) expense for the three months ended June 30, 2024 was $4,849,472, compared to $4,057,197 for the three months ended June 30, 2023, an increase of $792,275, or 20%. Despite a number of expense reduction strategies implemented in the three months ended June 30, 2024, this slight increase was primarily due to the timing of payments pursuant to the terms of a separation agreement with a former Company executive, changes in accounting policies that resulted in a non-cash expense of approximately $800,000 due to reclassifying capitalized intellectual property, and a 57% increase in share-based compensation over the three months ended June 30, 2024 compared to June 30, 2023 based on the timing of equity awards.

Current wording

General and administrative (“G&A”) expense for the nine months ended September 30, 2024 was $9,135,225, compared to $11,173,643 for the nine months ended September 30, 2023, a decrease of $2,038,418, or 18%. Despite one-time charges associated with the separation with a former Company executive and changes in accounting policies that resulted in a non-cash expense of approximately $800,000 due to reclassifying capitalized intellectual property, this slight decrease was primarily due to the implementation of expense reduction strategies by leadership in the nine months ended September 30, 2024, which significantly reduced travel expenses, the number of professional service providers and associated expenses, and reduced headcount and associated overhead of G&A staff from 13 employees at September 30, 2023 to 7 employees at September 30, 2024.

Previous wording

**Interest Income.**Interest income was $23,057 and $55,550 for the three months ended June 30, 2024, and 2023, respectively, representing a decrease of $32,493. The decrease was primarily due to lower cash balances held in interest bearing accounts for the three months ended on June 30, 2024 compared to the three months ended June 30, 2023.

Current wording

**Interest Income.**Interest income was $8,080 and $51,391 for the three months ended September 30, 2024, and 2023, respectively, representing a decrease of $43,311. The decrease was primarily due to lower cash balances held in interest bearing accounts for the three months ended September 30, 2024 compared to the three months ended September 30, 2023.

Previous wording

Interest income was $50,771 and $124,021 for the six months ended June 30, 2024, and 2023, respectively, representing a decrease of $73,250. The decrease was primarily due to lower cash balances held in interest bearing accounts for the six months ended on June 30, 2024 compared to the six months ended June 30, 2023.

Current wording

Interest income was $58,851 and $175,413 for the nine months ended September 30, 2024, and 2023, respectively, representing a decrease of $116,562. The decrease was primarily due to lower cash balances held in interest bearing accounts for the nine months ended September 30, 2024 compared to the nine months ended September 30, 2023.

Previous wording

**Depreciation Expense.**Depreciation expense was $2,288 and $3,837 for the three months ended June 30, 2024, and 2023, respectively, representing a decrease of $1,549, or 40%. The changes in associated depreciation expense for the three months ended June 30, 2024 were primarily due to the timing of purchases of computer equipment for new employees and changes to accounting policies related to depreciation.

Current wording

**Depreciation Expense.**Depreciation expense was $1,272 and $3,724 for the three months ended September 30, 2024, and 2023, respectively, representing a decrease of $2,452, or 66%. The change in depreciation expense for the three months ended September 30, 2024 was primarily due to the timing of purchases of computer equipment for new employees and changes to accounting policies related to depreciation.

Previous wording

Depreciation expense was $4,958 and $7,853 for the six months ended June 30, 2024, and 2023, respectively, representing a decrease of $2,895, or 37%. The changes in associated depreciation expense for the six months ended June 30, 2024 were primarily due to the timing of purchases of computer equipment for new employees and changes to accounting policies related to depreciation.

Current wording

Depreciation expense was $6,230 and $11,578 for the nine months ended September 30, 2024, and 2023, respectively, representing a decrease of $5,348, or 46%. The change in depreciation expense for the nine months ended September 30, 2024 was primarily due to the timing of purchases of computer equipment for new employees and changes to accounting policies related to depreciation.

Previous wording

Net Loss. We had a net loss of $6,495,845 and $7,980,193 for the three months ended June 30, 2024, and 2023, respectively, representing a decrease of $1,484,348, or 19%. The decrease in net loss between these periods was primarily due to the implementation of expense reduction strategies by leadership in the three months ended June 30, 2024, which reduced travel expenses, the number of professional service providers and associated expenses, and reduced headcount and associated overheads of overall Company staff from 30 employees at June 30, 2023 to 21 employees at June 30, 2024.

Current wording

Net Loss. We had a net loss of $4,315,987 and $7,748,243 for the three months ended September 30, 2024 and 2023, respectively, representing a decrease of $3,432,256, or 44%. The decrease in net loss between these periods was primarily due to the implementation of expense reduction strategies by leadership in the three months ended September 30, 2024, which reduced travel expenses, the number of professional service providers and associated expenses, and reduced headcount and associated overhead of overall Company staff from 31 employees at September 30, 2023 to 19 employees at September 30, 2024.

Previous wording

We had a net loss of $12,464,714 and $17,182,967 for the six months ended June 30, 2024, and 2023, respectively, representing a decrease of $4,718,253, or 27%. The decrease in net loss between these periods was primarily due to the implementation of expense reduction strategies by leadership in the six months ended June 30, 2024, which reduced travel expenses, the number of professional service providers and associated expenses, and reduced headcount and associated overheads of overall Company staff from 30 employees at June 30, 2023 to 21 employees at June 30, 2024.

Current wording

We had a net loss of $16,780,701 and $24,931,209 for the nine months ended September 30, 2024, and 2023, respectively, representing a decrease of $8,150,508, or 33%. The decrease in net loss between these periods was primarily due to the implementation of expense reduction strategies by leadership in the nine months ended September 30, 2024, which reduced travel expenses, the number of professional service providers and associated expenses, and reduced headcount and associated overhead of overall Company staff from 31 employees at September 30, 2023 to 19 employees at September 30, 2024.

Previous wording

From inception through June 30, 2024, we have never generated revenue from product sales and have incurred net losses in each year. As of June 30, 2024, we had an accumulated deficit of $146,152,994. We have funded our operations primarily through the sale and issuance of capital stock.

Current wording

From inception through September 30, 2024, we have never generated revenue from product sales and have incurred net losses in each year. As of September 30, 2024, we had an accumulated deficit of $150,468,981. We have funded our operations primarily through the sale and issuance of capital stock.

Previous wording

During the six months ended June 30, 2024, we (i) sold 169,033 shares of common stock for aggregate net proceeds of $902,647 pursuant to our 2023 ATM Facility (defined below), and (ii) completed a registered direct offering in which we sold (x) 165,000 shares of our common stock, (y) pre-funded warrants exercisable for up to an aggregate of 1,377,112 shares of our common stock (“March 2024 Pre-Funded Warrants”), and (z) warrants exercisable for up to an aggregate of 1,542,112 shares of our common stock (“March 2024 Common Warrants”), for net proceeds of approximately $5.8 million. In connection with the March 2024 registered direct offering, we amended certain existing warrants to reduce the exercise price and extend the term thereof. See also “Note 4 - Equity - Registered Direct Offerings” to our unaudited condensed financial statements included in this Quarterly Report on Form 10-Q. As of August 5, 2024, an aggregate of 598,112 March 2024 Pre-Funded Warrants had been exercised for shares of common stock.

Current wording

During the nine months ended September 30, 2024, we (i) sold 2,318,450 shares of common stock for aggregate net proceeds of $2,117,752 pursuant to our 2023 ATM Facility (defined below), and (ii) completed a registered direct offering in which we sold (x) 165,000 shares of our common stock, (y) pre-funded warrants exercisable for up to an aggregate of 1,377,112 shares of our common stock (“March 2024 Pre-Funded Warrants”), and (z) warrants exercisable for up to an aggregate of 1,542,112 shares of our common stock (“March 2024 Common Warrants”), for net proceeds of approximately $5.8 million. In connection with the March 2024 registered direct offering, we amended certain existing warrants to reduce the exercise price and extend the term thereof. See also “Note 4 - Equity - Registered Direct Offerings” to our unaudited condensed financial statements included in this Quarterly Report on Form 10-Q. As of September 30, 2024, all of the 1,377,112 March 2024 Pre-Funded Warrants had been exercised for shares of common stock.

Previous wording

As of June 30, 2024, we had $2,459,024 in cash and cash equivalents.

Current wording

As of September 30, 2024, we had $1,488,281 in cash and cash equivalents.

Previous wording

We do not expect to generate revenue from product sales unless and until we successfully complete development of, obtain regulatory approval for and begin to commercialize one or more of our current or potential product candidates, which we expect will take a number of years and which is subject to significant uncertainty. Accordingly, we anticipate that we will need to raise additional capital to fund our future operations, which include conducting our Acclaim-1 and Acclaim-3 clinical trials (of which both are currently enrolling) and completing preclinical work for potential other oncology candidates and completing preclinical work and conducting clinical trials for our diabetes program. We expect to complete the enrollment of the first 19 patients in the Phase 2a expansion portion of the Acclaim-1 trial in the first half of 2025. Enrollment in the Acclaim-3 clinical trial is expected to be completed during the second half of 2024 after which we expect to commence the Phase 2 portion of the Acclaim-3 trial in the second half of 2024. Until such time as we can generate substantial revenue from product sales, if ever, we expect to finance our operating activities through a combination of equity offerings, drawdowns on our ATM pursuant to our Agreement with the Agent, and debt financings and we may seek to raise additional capital through strategic collaborations or transactions. However, we may be unable to raise additional funds or enter into such arrangements when needed on favorable terms, or at all, which would have a negative impact on our financial condition and could force us to delay, limit, reduce or terminate our research and development programs or commercialization efforts or grant rights to others to develop or market product candidates that we would otherwise prefer to develop and market ourselves. Failure to receive additional funding could cause us to curtail or cease our operations. Furthermore, even if we believe we have sufficient funds for our current or future operating plans, we may seek additional capital due to favorable market conditions or strategic considerations. As a result of the Company's recurring losses from operations and the need for additional financing to fund its operating and capital requirements, there is uncertainty regarding the Company’s ability to maintain liquidity sufficient to operate its business effectively over the next 12 months, which raises substantial doubt as to the Company’s ability to continue as a going concern.

Current wording

We do not expect to generate revenue from product sales unless and until we successfully complete development of, obtain regulatory approval for and begin to commercialize one or more of our current or potential product candidates, which we expect will take a number of years and which is subject to significant uncertainty. Accordingly, we anticipate that we will need to raise additional capital to fund our future operations, which include conducting our Acclaim-1 and Acclaim-3 clinical trials (of which both are currently enrolling) and completing preclinical work for potential other oncology candidates and completing preclinical work and conducting clinical trials for our diabetes program. We expect to complete the enrollment of the first 19 patients in the Phase 2a expansion portion of the Acclaim-1 trial in the first half of 2025. We continue to anticipate completion of enrollment in the Phase 1 dose escalation portion of the Acclaim-3 clinical trial and to start the Phase 2 expansion portion of the trial in the second half of 2024, dependent on the number of patients needed to be enrolled in the 0.12 mg/kg dose group. Until such time as we can generate substantial revenue from product sales, if ever, we expect to finance our operating activities through a combination of equity offerings, drawdowns on our ATM pursuant to our Agreement with the Agent, and debt financings and we may seek to raise additional capital through strategic collaborations or transactions. However, we may be unable to raise additional funds or enter into such arrangements when needed on favorable terms, or at all, which would have a negative impact on our financial condition and could force us to delay, limit, reduce or terminate our research and development programs or commercialization efforts or grant rights to others to develop or market product candidates that we would otherwise prefer to develop and market ourselves. Failure to receive additional funding could cause us to curtail or cease our operations. Furthermore, even if we believe we have sufficient funds for our current or future operating plans, we may seek additional capital due to favorable market conditions or strategic considerations. As a result of the Company's recurring losses from operations and the need for additional financing to fund its operating and capital requirements, there is uncertainty regarding the Company’s ability to maintain liquidity sufficient to operate its business effectively over the next 12 months, which raises substantial doubt as to the Company’s ability to continue as a going concern.

Previous wording

Based on our current cash, we estimate that we will be able to fund our expenditure requirements for our current operations and planned clinical trial activities into September 2024. We have based these estimates on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we currently plan due to incorrect assumptions or due to a decision to expand our activities beyond those currently planned. We previously have experienced delays in engaging clinical sites as a result of disruptions at these clinical sites caused by the COVID-19 pandemic. We also have experienced delays in clinical trial enrollment as a result of competition for patients and additional time required in connection with our transition to the new third party CDMO and the manufacture of final drug product. Delays in the conduct of our trials could result in utilizing our capital resources sooner without advancing our clinical trials as anticipated.

Current wording

Based on our current cash, we estimate that we will be able to fund our expenditure requirements for our current operations and planned clinical trial activities into December 2024. We have based these estimates on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we currently plan due to incorrect assumptions or due to a decision to expand our activities beyond those currently planned. We previously have experienced delays in engaging clinical sites as a result of disruptions at these clinical sites caused by the COVID-19 pandemic. We also have experienced delays in clinical trial enrollment as a result of competition for patients and additional time required in connection with transitions to new third party CDMOs and the manufacture of final drug product. Delays in the conduct of our trials could result in utilizing our capital resources sooner without advancing our clinical trials as anticipated.

Previous wording

The following table sets forth the primary sources and uses of cash during the six months ended June 30, 2024, and 2023:

Current wording

The following table sets forth the primary sources and uses of cash during the nine months ended September 30, 2024, and 2023:

Previous wording

Net cash used in operating activities was $11,093,733 and $15,039,538 for the six months ended June 30, 2024, and 2023, respectively, a decrease of $3,945,805, or 26%. This decrease was primarily due to the implementation of expense reduction strategies by Company leadership in the six months ended June 30, 2024, which reduced travel expenses, the number of professional service providers and associated expenses, and reduced headcount and associated overheads of overall Company staff from 30 employees at June 30, 2023 to 21 employees at June 30, 2024.

Current wording

Net cash used in operating activities was $13,279,658 and $19,774,740 for the nine months ended September 30, 2024, and 2023, respectively, a decrease of $6,495,082, or 33%. This decrease was primarily due to the implementation of expense reduction strategies by Company leadership in the nine months ended September 30, 2024, which reduced travel expenses, the number of professional service providers and associated expenses, and reduced headcount and associated overheads of overall Company staff from 30 employees at September 30, 2023 to 19 employees at September 30, 2024.

Previous wording

Net cash provided by investing activities was $1,167 for the six months ended June 30, 2024, compared to net cash used in investing activities of $39,627 for the six months ended June 30, 2023, or a net change of $40,794. This difference in period-over-period net cash provided by (used in) investing activities was primarily due to timing associated with filing and patent prosecution costs of our intellectual property.

Current wording

Net cash provided by investing activities was $1,167 for the nine months ended September 30, 2024, compared to net cash used in investing activities of $61,383 for the nine months ended September 30, 2023, or a net change of $62,550. This difference in period-over-period net cash provided by (used in) investing activities was primarily due to timing associated with filing and patent prosecution costs of our intellectual property.

Previous wording

Net cash provided by financing activities was $6,813,961 and $4,080,780 during the six months ended June 30, 2024, and 2023, respectively. This increase of $2,733,181 was primarily due to differences in amounts raised by sales of common stock in capital raising activities conducted during the six months ended June 30, 2024, and 2023, respectively.

Current wording

Net cash provided by financing activities was $8,029,143 and $10,593,373 during the nine months ended September 30, 2024, and 2023, respectively. This decrease of $2,564,230 was primarily due to differences in amounts raised by sales of our securities in capital raising activities conducted during the nine months ended September 30, 2024, and 2023, respectively.