BriaCell Therapeutics Corp

ITEM BUSINESS

Overview of the Company

BriaCell Therapeutics Corp. (“Briacell” or the “Company”) is a clinical-stage biotechnology company that is developing novel immunotherapies to transform cancer care. Immunotherapies have come to the forefront in the fight against cancer as they harness the body’s own immune system to recognize and destroy cancer cells. The Company is currently advancing its Bria-IMT™ targeted immunotherapy in combination with an immune check point inhibitor (Retifanlimab) in a pivotal 1 Phase 3 study in metastatic breast cancer (listed on ClinicalTrials.gov asNCT06072612). Bria-IMT™ is currently under Fast Track Designation by the U.S. Food and Drug Administration (the “FDA”) intended to accelerate the review process of novel treatments that address unmet medical needs. Positive completion of the pivotal study, following review by FDA, could lead to full approval of the Bria-IMT™ immune checkpoint inhibitor combination in metastatic breast cancer. BriaCell has reported benchmark-beating patient survival and clinical benefit in metastatic breast cancer with median overall survival of 13.4 months in BriaCell’s metastatic breast cancer patients vs. 6.7-9.8 months 2 for similar patients reported in the literature in its Phase 2 study of Bria-IMT™ combination study with retifanlimab. Additionally, BriaCell reported median overall survival of 16.5 months in Phase 2 Bria-IMT™ study patients treated in combination with immune checkpoint inhibitor in patients treated with the Phase 3 formulation since 2022 (post-COVID). A completed Bria-IMT™ Phase 1/2 combination study with retifanlimab (an anti-PD1 antibody manufactured by Incyte) confirmed tolerability and early-stage efficacy (listed on ClinicalTrials.gov asNCT03328026).

BriaCell Phase 1/2 Study of Bria-OTS™, BriaCell’s personalized off-the-shelf immunotherapy, also known as Bria-BRES™, in metastatic breast cancer is ongoing (listed on ClinicalTrials.gov asNCT06471673). The first patient treated with 4 inoculations of cells (single agent) demonstrated complete resolution of a lung metastasis. BriaCell is currently developing Bria-OTS™ and its advanced form, Bria-OTS+™, as a platform technology for personalized off-the-shelf immunotherapies for numerous types of cancer. In September 2024, the Company announced BriaCell had received positive feedback from its Pre-Investigational New Drug Application (Pre-IND) meeting with FDA for Bria-PROS+™ for prostate cancer.

Market

It is estimated by the National Cancer Institute Cancer Facts and Figures that in 2025, approximately 319,750 people (316,950 women and 2,800 men) will be diagnosed with breast cancer in the United States. That means that every two minutes an American woman is diagnosed with breast cancer and more than 42,170 are projected to die in 2025. Although about 100 times less common than in women, breast cancer also affects men. It is estimated that the lifetime risk of men getting breast cancer is about 1 in 1,000, and the American Cancer Society estimates that approximately 2,800 new cases of invasive male breast cancer will be diagnosed and approximately 510 men will die from breast cancer in 2025.

According to the May 2025 “Global Oncology Trends 2025” report by the IQVIA Institute, the global market for cancer drugs (including immunotherapy drugs) is expected to reach nearly $441 billion by the end of 2029.

1“Pivotal” is an industry term referring to a Phase 3 clinical study intended to show and confirm the safety and efficacy of a treatment.

2 Cortes J, et al. Annals of Oncology 2018; Kazmi S, et al. Breast Cancer Res Treat. 2020 Aug 17; O’Shaughnessy J et al. Breast Cancer Res Treat. 2022; Tripathy D, et al. JAMA Oncol. 2022

About 13% percent of women will be diagnosed with breast cancer at some point during their lifetime. In 2025, over 4 million women were living with female breast cancer in the United States. Approximately 83% of cases present as invasive breast cancer. Approximately 6% of new breast cancer diagnoses are Stage IV (metastatic breast cancer (“MBC”), which has already spread to other organs). Twenty to thirty percent of all women diagnosed with breast cancer will develop MBC. Breast cancer can be subdivided based on receptor status - the hormone receptors for estrogen (ER) and progesterone (PR), collectively referred to as hormone receptors (HR), and the Her2/neu growth factor receptor (HER2). Based on the latest SEER statistics, 68% were found to be HR+/HER2−, 10% were triple-negative (HR−/HER2−), 10% were HR+/HER2+, and 4% were HR−/HER2+.1

It is estimated that over 150,000 women in the US were living with MBC in 20152 and this is projected to increase to over 240,000 by 2030. For those with metastatic disease at diagnosis, their 5-year survival rate is 30%.1 For patients who develop MBC after initially having localized disease, if they had a good response to treatment (i.e. a disease-free interval of more than 24 months), their survival rate is similar to that of patients with MBC at initial diagnosis, but if their disease-free interval is less than 24 months, their prognosis is worse.4 We currently propose that Bria-IMT’s™ indication will be for the treatment of patients with MBC who have no approved alternative therapies available. Similarly, another study showed that the median overall survival among patients with de novo stage IV MBC was 39.2 months, while for patients with relapsed disease it was 27.2 months.5 Median progression free survival after first-line therapy is only 9 months and the survival benefit decreases with subsequent lines of therapy.6 One study showed that of 386 patients with MBC, 374 (97%) received first-line therapy, 254 (66%) received second-line therapy, 175 (45%) received third-line therapy, and 105 (27%) received therapy beyond third-line.7 More recent data indicates that for patients with MBC who have received 2 or more prior lines of therapy, median survival is 5.9-9.8 months.

1 See https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/2022-2024-breast-cancer-fact-figures-acs.pdf

2 Mariotto AB, Etzioni R, Hurlbert M, Penberthy L, Mayer M. Estimation of the Number of Women Living with Metastatic Breast Cancer in the United States. Cancer Epidemiol Biomarkers Prev. 2017 Jun;26(6):809-815.

3 Breast Cancer Facts & Figures 2017-2018. Atlanta: American Cancer Society, Inc. 2017.

4 Lobbezoo, D. J. A. et al. Prognosis of metastatic breast cancer subtypes: the hormone receptor/HER2-positive subtype is associated with the most favorable outcome. Breast Cancer Res. Treat. 141, 507-514 (2013).

5 Dawood S, Broglio K, Ensor J, Hortobagyi GN, Giordano SH. Survival differences among women with de novo stage IV and relapsed breast cancer. Ann Oncol. 2010 Nov; 21(11):2169-74.

6 Bonotto M, Gerratana L, Iacono D, Minisini AM, Rihawi K, Fasola G, Puglisi F. Treatment of Metastatic Breast Cancer in a Real-World Scenario: Is Progression-Free Survival With First Line Predictive of Benefit From Second and Later Lines? Oncologist.

7 Kotsakis A, Ardavanis A, Koumakis G, Samantas E, Psyrri A, Papadimitriou C. Epidemiological characteristics, clinical outcomes and management patterns of metastatic breast cancer patients in routine clinical care settings of Greece: Results from the EMERGE multicenter retrospective chart review study. BMC Cancer. 2019 Jan 18;19(1):88.

For further information on our lead candidate Bria-IMT™ clinical development, see “Bria-IMT™” in the “Production /Pipeline” section.

Competition

Currently available therapeutic options for breast cancer offer some hope for patients, but there is much room for improvement. Evaluating response rates (partial and complete responses = ORR), progression free survival (“PFS”) and overall survival (“OS”) from recent clinical trials in similar late-stage subjects with metastatic or recurrent breast cancer indicate that response rates range from 3-5% with PFS from 1.6 to 2.3 months 1, and OS from ~7 to 14 months 2.

MBC treated with second or higher lines of therapy has a very poor prognosis and few effective therapies that consistently induce long-term remission, which indicates the market demand and clinical need for new and improved therapeutic drugs and treatment options in order to improve these response outcomes and patient survival rates. Thus, Bria-IMT™ has the potential to induce long-term remission, especially in combination with immunotherapies.

There are a number of cancer vaccines in development for breast cancer, including but not limited to TPIV200 (Marker Therapeutics, Inc.), AE-37 (Antigen Express), and Stimuvax (Merck KgA). While these development candidates are aimed at a number of different targets, and AE-37 has published data in the HER2 breast cancer patient population, there is no guarantee that any of these compounds will not in the future be indicated for treatment of low-to-intermediate HER2 breast cancer patients and become directly competitive with Bria-IMT.

1 Bardia A, et al. J Clin Oncol. 2024 May 20;42(15):1738-1744; Tripathy D, et al. JAMA Oncol. 2022 Nov 1;8(11):1700-1701; O’Shaughnessy J, et al. Breast Cancer Res Treat. 2022 Sep;195(2):127-139.

2 Rugo, H. S., et al. The Lancet, 402(10411), 1423–1433; Bardia A, et al. J Clin Oncol. 2024 May 20;42(15):1738-1744.

While there are many biotech companies working to create an effective breast cancer therapeutic vaccine, a significant gap remains in the effectiveness and safety of second or higher lines of therapy. The most studied targeted immunotherapy, Neuvax (Galena), a HER2 peptide vaccine, failed a Phase III trial, but there is encouraging data to support at least three ongoing clinical trials combining trastuzumab with HER2 epitope immunogens.1 The National Cancer Institute (“NCI”) randomized trial adding PANVAC (a poxviral-based immunogen) to docetaxel increased the median PFS from 3.9 months to 7.9 months and is to be used as a basis for larger, more sophisticated clinical trials.2 An immunogen targeting a carbohydrate antigen, globo-H, was associated with improved PFS, but only in the subset able to mount antibody responses.3 A Johns Hopkins breast cancer trial using a breast cancer cell line transfected with the gene for GM-CSF has not been positive but, using the same cell line with trastuzumab, 40% of patients enjoyed clinical benefit (CR+PR+stable) at one year.4 Finally, the study of targeted cancer immunotherapies in combination with other therapies is receiving much attention, particularly combination with checkpoint inhibitors.5

There are several other approaches to developing targeted breast cancer immunotherapies. These include using peptide cocktails, a triple peptide regimen, recombinant HER2, antigen-pulsed dendritic cells, DNA immunogens, whole cell allogeneic GM-CSF secreting SKBR3 or T47D cells, an (HLA)-A2/A3-restricted immunogenic peptide derived from the HER2 protein, oxidized mannan-MUC1, and personalized peptide immunogens.

Among the most promising results in patients with advanced disease have been using whole-cell preparations, particularly if the cells are engineered to express GM-CSF. We are taking this approach and capitalizing on positive initial results with Bria-IMT™ monotherapy in difficult to treat patients using a regimen that both limits regulatory T cell activity (using low dose cyclophosphamide pre-treatment) and boosts the immune response (using post-dose alpha interferon in the inoculation sites). The combination with PD-1 inhibitors is a logical extension of our findings where 21 of 23 MBC patients had demonstrable PD-L1 expression on the circulating tumor cells (“CTCs”) and/or circulating cancer-associated macrophage-like cells (“CAMLs”). The overall strategy, once the initial milestones have been met, to enroll additional patients for product registration, will allow rapid progression of the best therapeutic option to a Biologics License Application (“BLA”).

Cancer immunotherapy has become a significant growth area for the biopharmaceutical industry, attracting large pharmaceutical companies as well as small niche players. Generally, our principal competitors in the cancer immunotherapy market comprise both companies with currently approved products for various indications, such as manufacturers of approved bispecific antibodies, CAR-T cells, and checkpoint inhibitors, as well as companies currently engaged in cancer immunotherapy clinical development. The large and medium-size players who have successfully obtained approval for cancer immunotherapy products include Bristol-Myers Squib Company, Merck & Co., Inc., Genentech, Inc. (a subsidiary of Roche Holding AG), AstraZeneca PLC, Celgene Corporation, Johnson & Johnson/Janssen Pharmaceuticals, Amgen, Novartis, Acerta Pharmaceuticals (a subsidiary of AstraZeneca), Juno Therapeutics, Inc. (a subsidiary of Celgene), Kite Pharma, Inc., a wholly-owned subsidiary of Gilead Sciences, Inc. and Pfizer, Inc./EMD Serono, Inc. Most of these companies, either alone or together with their collaborative partners, have substantially greater financial resources than does BriaCell.

Companies developing novel products with similar indications to those we are pursuing are expected to influence our ability to penetrate and maintain market share. For patients with early-stage breast cancer, adjuvant therapy is often given to prevent recurrence and increase the chance of long-term disease-free survival. Adjuvant therapy for breast cancer can include chemotherapy, hormonal therapy, radiation therapy, or combinations thereof. In addition, the HER2 targeted drug trastuzumab (HERCEPTIN), alone or in combination with pertuzumab (PERJETA), both manufactured and marketed by Roche/Genentech, may be given to patients with tumors with high expression of HER2 (IHC 3+), as well as other novel targets such as MUC1, which may be useful in treating breast cancer. In addition, the FDA approved the first ever immunotherapy regimen for breast cancer to the Roche/Genentech PD-L1 checkpoint inhibitor atezolizumab (TECENTRIQ), combined with Celgene’s nab-paclitaxel (ABRAXANE) for TNBC that cannot be removed with surgery and is locally advanced or metastatic.

Many of our competitors, either alone or with their strategic partners, have substantially greater financial, technical and human resources than we do, and also have greater experience in obtaining FDA and other regulatory approvals of treatments and commercializing those treatments. Accordingly, our competitors may be more successful than us in obtaining approval for cancer immunotherapy products and achieving widespread market acceptance. Our competitors’ treatments may be more effectively marketed and sold than any products we may commercialize, thus causing limited market share before we can recover the expenses of developing and commercializing of our cancer immunotherapy product candidate.

1 Mittendorf, E. A.; Peoples, G. E., Injecting Hope-A Review of Breast Cancer Vaccines. Oncology (Williston Park) 2016, 30 (5), 475-81, 485.

2 Heery, C. R.; Ibrahim, N. K.; Arlen, P. M.; Mohebtash, M.; Murray, J. L.; Koenig, K.; Madan, R. A.; McMahon, S.; Marte, J. L.; Steinberg, S. M.; Donahue, R. N.; Grenga, I.; Jochems, C.; Farsaci, B.; Folio, L. R.; Schlom, J.; Gulley, J. L., Docetaxel Alone or in Combination With a Therapeutic Cancer Vaccine (PANVAC) in Patients With Metastatic Breast Cancer: A Randomized Clinical Trial. JAMA Oncol 2015, 1 (8), 1087-95.

3 Huang, C.; Yu, A.; Tseng, L., Randomized phase II/III trial of active immunotherapy with OPT-822/OPT-821 in patients with metastatic breast cancer. J Clin Oncol 2016, 34 (15).

4 Chen, G.; Gupta, R.; Petrik, S.; Laiko, M.; Leatherman, J. M.; Asquith, J. M.; Daphtary, M. M.; Garrett-Mayer, E.; Davidson, N. E.; Hirt, K.; Berg, M.; Uram, J. N.; Dauses, T.; Fetting, J.; Duus, E. M.; Atay-Rosenthal, S.; Ye, X.; Wolff, A. C.; Stearns, V.; Jaffee, E. M.; Emens, L. A., A feasibility study of cyclophosphamide, trastuzumab, and an allogeneic GM-CSF-secreting breast tumor vaccine for HER2+ metastatic breast cancer. Cancer Immunol Res 2014, 2 (10), 949-61.

5 McArthur, H. L.; Page, D. B., Immunotherapy for the treatment of breast cancer: checkpoint blockade, cancer vaccines, and future directions in combination immunotherapy. Clin Adv Hematol Oncol 2016, 14 (11), 922-933.

Mergers and acquisitions in the biotechnology and pharmaceutical industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These activities may lead to consolidated efforts that allow for more rapid development of cancer immunotherapy product candidates.

These competitors also compete with us in recruiting and retaining qualified scientific and management personnel, the ability to work with specific clinical contract organizations due to conflicts of interest, and the conduct of trials in the ability to recruit clinical trial sites and subjects for our clinical trials.

We expect any products that we develop and commercialize to compete on the basis of, among other things, efficacy, safety, price and the availability of reimbursement from government and other third-party payors. Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are viewed as safer, more convenient or less expensive than any products that we may develop. Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for our current product candidates or any other future product candidate, which could result in our competitors establishing a strong market position before we are able to enter the market.

Products/Pipeline

Bria-IMT™

About Bria-IMT ™

Bria-IMT™, BriaCell’s lead candidate, is a whole-cell immunotherapy for metastatic breast cancer. Bria-IMT™ in combination with an immune check point inhibitor is undergoing pivotal Phase 3 clinical testing in patients with advanced MBC patients who have failed prior lines of therapy. The pivotal Phase 3 combination study is listed on ClinicalTrials.gov asNCT06072612.

Mechanism of Action of Bria-IMT™

Bria-IMT™ (SV-BR-1-GM) is a targeted immunotherapy for the treatment of breast cancer. Bria-IMT™ is a genetically engineered human breast cancer cell line with features of immune cells and clinically applied as a targeted immunotherapy. Bria-IMT™ immunotherapy is derived from a grade II (moderately differentiated) tumor which activates the immune system to attack and destroy breast cancer tumors.

Bria-IMT™ is designed to secrete GM-CSF, a factor that stimulates components of the immune system. Specifically, GM-CSF activates dendritic cells, the cells that start immune responses. These activated dendritic cells then activate T cells, a key component of the immune system, to recognize the tumor cells as foreign, and eliminate them. To amplify this action, we have combined Bria-IMT™ with other immune system activators including cyclophosphamide (used in low doses to reduce immune suppression), and low-dose local interferon-α, a cytokine that further activates the immune system. This is termed the Bria-IMT™ regimen. We believe this approach of simultaneous activation of the immune system via different pathways will improve the immune system response to attack and destroy cancer cells.

Phase 1/2 Clinical Trial of the Bria-IMT™ regimen in Advanced Metastatic Breast Cancer

BriaCell conducted Phase 1/2a clinical trials (SVMC #01-026 and WRI-GEV-007) of the Bria-IMT™ regimen in patients with advanced breast cancer. In the 2 studies a total of 27 patients were treated. They had failed on the average (median) 5 prior lines of therapy. The treatment was generally well tolerated with local irritation at the inoculation sites the main adverse event judged at least possibly related to study medication. In total, 18 patients were evaluable (had measurable disease and both baseline and on treatment imaging studies). The efficacy data is shown here.

In this study it was also noted that in 21 of 23 patients with circulating tumor cells or cancer-associated macrophage-like cells expressed PD-L1, and immune checkpoint that blocks the activity of activated T cells to kill tumor cells. This led to the design of a combination study where the Bria-IMT™ regimen is given in combination with an immune checkpoint inhibitor (CPI).

Phase 1/2 Clinical Trial of Bria-IMT™ in Combination with Immune Check Point Inhibitors in Advanced Metastatic Breast Cancer

BriaCell has been conducting a Phase 1/2a clinical trial (BRI-ROL-001) of Bria-IMT™, in combination with immune checkpoint inhibitors such as pembrolizumab (KEYTRUDA®; manufactured by Merck & Co., Inc.) and retifanlimab, an immune checkpoint inhibitor manufactured by Incyte. The combination study is listed in ClinicalTrials.gov asNCT03328026 under FDA-approved BB-IND 10312 under protocol BRI-ROL-001 at ten clinical sites throughout the United States. The study is now closed to enrollment.

In the Phase 1 part of the study, the Bria-IMT™ regimen was dosed in combination with Keytruda ® in 11 patients and in 11 patients with retifanlimab, with one patient starting on the combination with Keytruda® and crossing-over to the combination with retifanlimab. In the Phase 2 part of the study an additional 32 patients were dosed (54 patients total). In Phase 2 part of the study, the Bria-IMT™ regimen is being dosed in combination with retifanlimab with patients randomized to either receive the Bria-IMT™ regimen first (16 patients) or retifanlimab first (16 patients).

BriaCell also evaluated 2 formulations of Bria-IMT, one treated with interferon gamma and one untreated.

The design of the study is shown here.

The patients had advanced breast cancer as shown here.

Treatment with the combination regimen was generally well tolerated as shown here.

There was no statistically significant difference in Progression Free Survival (PFS) based on order of administration (CPI in cycle 1 or delayed to cycle 2). There was a significant effect of PFS of formulation as shown here.

Data presented at ASCO 2024 see Calfa et al. Journal of Clinical Oncology 42, 6_suppl

https://doi.org/10.1200/JCO.2024.42.16_suppl.1022

The overall survival of the patients for all patients on this study has been evaluated in an ongoing fashion. Since the study was largely on hold during COVID (2020 and 2021), patients dosed in 2019 and 2020 have been followed for a longer time. Therefore survival data has been evaluated for patients dosed before 2022 and since 2022. This should be considered in the context of clinical studies in patients with metastatic breast cancer who have failed at least 2 prior regimens 1.

The Bria-IMT™ regimen, using the Phase 3 formulation, with a CPI has shown a median overall survival (OS) of 13.4 months for all patients by the Kaplan Meier method, as shown in the Figure below. For patients treated since 2022, the median OS was estimated at 16.5 months.

Figure B. Overall Survival of Patients with Metastatic Breast Cancer treated with the Bria-IMT™ regimen using the Phase 3 formulation with a CPI.

Update of data presented at the 2024 San Antonio Breast Cancer Symposium

ClinicalTrials.gov ID NCT03328026

1 Cortes J, et al. Annals of Oncology 2018; Kazmi S, et al. Breast Cancer Res Treat. 2020 Aug 17; O’Shaughnessy J et al. Breast Cancer Res Treat. 2022; Tripathy D, et al. JAMA Oncol. 2022

In its Phase 2 study of Bria-IMT plus check point inhibitors (CPI), outperformed ADC drugs in hormone receptor positive (HR+) metastatic breast cancer (MBC) patients. In BriaCell’s Phase 2 clinical study in late-stage MBC, 25 of 37 patients treated with the ongoing pivotal Phase 3 Bria-IMT formulation were identified as having HR+ breast cancer. As shown in Table 1, the survival data of these 25 patients (17.3 months) exceeds those of the current ADC standard of care TRODELVY® (14.4 months) and those treated with chemotherapy (11.3 months). The survival data for the Bria-IMT regimen + immune check point inhibitor in the triple negative breast cancer (TNBC), characterized by the absence of estrogen (ER), progesterone (PR) and human epidermal growth factor (HER2) receptors, was also better than TRODELVY® and markedly higher than those of chemotherapy.

Table 1: Comparable Analysis of median overall survival (estimated using the Kaplan-Meier method) for the BriaCell Phase 2 study of BriaCell’s Bria-IMT™ plus CPI versus other drugs in MBC patient subsets.

• Patients treated with the Phase 3 formulation

** Number of prior chemotherapy-containing regimens

HR+: hormone receptor-positive

TNBC: Triple-negative breast cancer (lacks the estrogen receptor, progesterone receptor, and lacks or has low levels of human epidermal growth factor receptor 2 (HER2))

BriaCell has also analyzed the data from the Phase 1/2 study in patients who have failed prior ADC therapy. The results are shown here in comparison to studies of comparable patients in the literature.

Compared with 7-10% in comparable patients treated with best available therapy (the comparator for Phase 3)

During the course of this study, BriaCell has had several remarkable responders. The data for 2 of them is shown here.

Patient 06-005 had failed 13 prior regimens. She had baseline breast cancer metastases behind the left eye (orbit), in the outside lining of the brain (dura mater) and the adrenal gland. Following 6 months of treatment the orbital tumor completely resolved and the others improved. She was judged an overall partial responder.

Imaging for Patient 06-005

Patient 11-018 had failed 8 prior regimens including the ADC Enhertu®. She had a right orbital tumor causing extensive proptosis (eye bulging) & brain (temporal lobe) metastasis. There was a complete resolution of the temporal lobe metastasis and a marked reduction in the orbital lesion with resolution of proptosis and improvement in eye pain. She has been on the study for >21 months.

Imaging for Patient 11-018

Overall BriaCell has treated 7 patients with intracranial (inside the skull) metastatic disease who had measurable disease. The intracranial overall response rate (iORR) is 71%, which compares very favorably with the data for comparable patients in the literature. Some of this data is shown here.

Intracranial responses for patients treated with Bria-IMT™

Note that the iORR in comparable patients typically <20%. (see Niwinska A, Pogoda K, Jagiello-Gruszfeld A, Duchnowska R. Intracranial Response Rate in Patients with Breast Cancer Brain Metastases after Systemic Therapy. Cancers (Basel). 2022 Feb 15;14(4):965 and Tripathy D, Tolaney SM, Seidman AD, Anders CK, Ibrahim N, Rugo HS, Twelves C, Diéras V, Müller V, Du Y, Currie SL, Hoch U, Tagliaferri M, Hannah AL, Cortés J; ATTAIN Investigators. Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase III ATTAIN Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1047-1052.)

Phase 3 Clinical Trial of Bria-IMT™ in Combination with Immune Check Point Inhibitors in Advanced Metastatic Breast Cancer compared with Treatment of Physician’s Choice (Bria-ABC)

BriaCell has been conducting a Phase 3 clinical trial (Bria-ABC) of Bria-IMT™, in combination with immune checkpoint inhibitor retifanlimab, an immune checkpoint inhibitor manufactured by Incyte. The combination study is listed in ClinicalTrials.gov asNCT06072612under FDA-approved BB-IND 10312. The primary endpoint is overall survival.

Bria-IMT™ is currently under Fast Track Designation by the FDA intended to accelerate the review process of novel treatments that address unmet medical needs. Positive completion of the pivotal study, following review by the FDA, could lead to full approval of the Bria-IMT™ immune checkpoint inhibitor combination in advanced metastatic breast cancer.

The FDA has agreed that improvement in overall survival in the Bria-IMT™ combination arm as compared to the physician’s choice of treatment arm will be the primary endpoint of the study. The study is expected to enroll 177 patients in the Bria-IMT™ combination therapy arm and 177 patients in the treatment of physician’s choice arm. To gather additional information on the Bria-IMT™ regimen alone, 50 patients are expected to be enrolled in this regimen and will be eligible for combination therapy following their initial post treatment evaluation. These patients will not be included in the primary analysis. The study will have an interim evaluation for efficacy which could result in early completion of the study. We expect frequent and responsive FDA communication under our Fast Track status during our pivotal Phase 3 study. The overall design of the study is shown here.

The first interim analysis will be at 144 events (mortalities). If the hazard ratio (HR) is ≤ 0.6, BriaCell will submit a Biologics Licensing Application (BLA). If the HR is > 0.6, the study will continue to completion with HR target of 0.7. Either of these could result in full approval of the Bria-IMT™ CPI combination regimen in advanced metastatic breast cancer.

The successful completion of the pivotal study would allow BriaCell to subsequently submit a Biologics License Application and accelerate the path to commercialization. The Phase 3 study has multiple locations throughout the USA as noted in the ClinicalTrials.gov listing https://clinicaltrials.gov/study/NCT06072612.

On December 2, 2024, March 20, 2025, and June 24, 2025, BriaCell announced that the Data Safety Monitoring Board (DSMB), an independent group of experts who review and monitor safety data of a clinical study to determine if a study should continue, be modified, or be halted early, had completed its first, second, and third reviews of safety events in patients enrolled in BriaCell’s pivotal randomized Phase 3 study of Bria-IMT™ plus an immune checkpoint inhibitor (CPI) combination regimen (ClinicalTrials.gov NCT06072612) in metastatic breast cancer. The Data Safety Monitoring Board (DSMB) stated no safety concerns, and recommended continuation of BriaCell’s pivotal Phase 3 study of Bria-IMT™ plus a CPI in MBC.

On April 22, 2025, the Company announced its ongoing pivotal Phase 3 clinical study (listed on ClinicalTrials.gov as NCT06072612) has consented over 100 and has enrolled over 75 patients. BriaCell anticipates reporting top line data as early as H1-2026.

On April 30, 2025, BriaCell reported “Late-Breaker” Phase 3 data at AACR 2025. Positive tolerability profile and potential response biomarkers were identified. Phase 3 clinical data showed potential predictive biomarkers for treatment response, first identified in the Phase 2 study. Biomarkers could be utilized to predict and provide better patient outcomes, including response rates and survival benefits. Positive delayed-type hypersensitivity (DTH) (p = 0.001) and a favorable Neutrophil-to-Lymphocyte Ratio (NLR) (p = 0.02) were linked to longer progression-free survival (PFS) in Phase 3 patients. Presence of Circulating Tumor Cells (CTC) after patients’ initial Phase 3 treatment supports their role as negative prognostic marker (p = 0.04). The Bria-IMT Phase 3 regimen was well-tolerated with a preferred tolerability profile.

Collaboration with Prevail InfoWorks, Inc.

In collaboration with Prevail InfoWorks, Inc. (“InfoWorks”), a Philadelphia, PA based contract research organization, BriaCell continues to recruit additional sites to speed up the patient recruitment process. BriaCell has signed a Master Service and Technology Agreement (“MSTA”) agreement with InfoWorks to provide clinical services and technologies for BriaCell’s upcoming pivotal study in advanced metastatic breast cancer. Services include clinical site coordination, project management, clinical monitoring and pharmacovigilance (safety management) services, and the use of InfoWork’s integrated real-time data analytics platform, The Single Interface ®, for clinical support and real-time data analysis.

In May 2023, Prevail Partners, LLC (“Prevail Partners”), an investment fund and affiliate of InfoWorks invested $4 million in the company at a 20% premium to the trailing thirty (30) trading day volume-weighted average price of the common shares of the Company on the Nasdaq Stock Exchange.

Manufacturing

We do not own or operate manufacturing facilities for the production of our product candidates, nor do we have plans to develop our own manufacturing operations in the foreseeable future. We currently depend on third-party contract manufacturers for all of our required raw materials, active pharmaceutical ingredients, and finished product candidate for our clinical trials. We currently employ internal resources and third-party consultants to manage our manufacturing contractors.

Bria-IMT™ is currently manufactured under current Good Manufacturing Practices (“cGMP”) pursuant to agreements with UC Davis and with FujiFilm Diosynth Biotechnology (“Fuji”), which is located in Thousand Oaks, California.

On June 11, 2015, the Company entered into an Agreement for Services with The Regents of the University of California, acting for and on behalf of UC Davis, pursuant to which UC Davis manufactures Bria-IMT™ (previously known as BriaVax) at its GMP facility. The Company pays UC Davis certain hourly rates depending on the specific services provided by UC Davis in connection with its manufacturing of Bria-IMT™.

On July 5, 2022, BriaCell announced that it had entered into a manufacturing service agreement with Waisman Biomanufacturing at the University of Wisconsin-Madison (“Waisman”), to manufacture Bria-Pros™, BriaCell’s off-the-shelf personalized immunotherapy for prostate cancer, for anticipated use in clinical studies. Waisman is a leading contract manufacturing organization with experience in the manufacturing of cellular therapies for clinical trials. Under the terms of the agreement, Waisman will be responsible for GMP manufacturing of Bria-Pros™ for anticipated use in clinical studies. Waisman’s expert team will be working closely with BriaCell’s scientific and product development teams to ensure timely production of Bria-Pros™ in compliance with applicable regulatory requirements by the FDA.

Pursuant to the Company’s master services agreement with Fuji, dated May 29, 2023, to manufacture Bria-IMT™, for anticipated use in clinical studies including the Phase 3 study. Fuji is a leading contract manufacturing organization with experience in the manufacturing of cellular therapies for clinical trials. Under the terms of the agreement, Fuji will be responsible for GMP manufacturing of Bria-IMT™ for anticipated use in clinical studies. Fuji’s expert team will be working closely with BriaCell’s scientific and product development teams to ensure timely production of Bria-IMT™ in compliance with applicable regulatory requirements by the FDA.

Production and Marketing Plan

Bria-IMT™ cells grow in simple tissue culture media and are irradiated prior to inoculation. Bria-IMT™ manufacturing will be performed by Contract Manufacturing Organizations. We have been working with FUJIFILM Diosynth Biotechnologies (“Fuji”) and the University of California, Davis Health System (“UC Davis”) GMP facility, who have developed a frozen formulation where the cells are grown, harvested and irradiated, followed by cryopreservation in a viable state. The cells are stockpiled and shipped directly to clinical sites for inoculation. Each lot of Bria-IMT™ is tested for potency (i.e. GM-CSF production), identity (i.e. HER2+ and ER/PR-) and adventitious agents to rule out contamination with infectious agents. To date, there have been no issues with these tests. Additional manufacturing facilities have been evaluated and may be enlisted as demand grows.

Marketing will target oncologists who are well-versed in the use of immunotherapy and especially breast cancer treatment centers. The initial target will be patients with metastatic or recurrent breast cancer who have failed at least two prior treatment regimens. We plan to develop the clinical data for Bria-IMT™ and to use this information to reach out to oncologists seeking additional therapeutic options for their patients. We will include in this effort a physician education campaign targeting the oncologists most likely to treat metastatic breast cancer. As these physicians become more aware of the data regarding Bria-IMT™ in breast cancer, we will make sure they also understand how best to use Bria-IMT™ in combination with other therapies that have complementary synergistic mechanisms of action. This will also come from the clinical studies described above focusing on combination therapy. Partnering with other pharmaceutical companies in order to market a number of drugs is also an option that we intend to pursue. Our eventual goal is to reach all oncologists who treat late stage breast cancer, either by direct outreach or by partnering with another company that has an established presence in the oncology space.

Bria-OTS™

Bria-OTS™: Personalized Off-the-Shelf Immunotherapy

BriaCell Phase 1/2 Study of Bria-OTS™, also known as Bria-BRES™, in metastatic breast cancer is open. The Phase 1/2 clinical study is listed on ClinicalTrials.gov as NCT06471673.

Development of Additional Immunotherapy Cell Lines

Bria-OTS™, the Company’s personalized, off-the-shelf immunotherapy, advanced meaningfully during the reporting period.

On November, 21, 2024, the Company announced that the first patient was dosed in its Phase 1/2 study (ClinicalTrials.gov identifier: NCT06471673) to evaluate the safety and efficacy of Bria-OTS™, BriaCell’s personalized next generation immunotherapy. The study will investigate Bria-OTS™ alone and in combination with immune check point inhibitor tislelizumab® (manufactured and supplied by BeiOne, Ltd.) for the treatment of metastatic breast cancer. Bria-OTS™ is an enhanced form of Bria-IMT™, currently in pivotal Phase 3 study for metastatic breast cancer.

On February 3, 2025, the Company announced a clinical response including resolution of a lung metastasis (breast cancer tumor that spread to the lung) with stable disease elsewhere in the first metastatic breast cancer (MBC) patient treated with Bria-OTS™ as a single agent. Bria-OTS™ is a personalized off-the-shelf immunotherapy, currently under investigation in a Phase 1/2a dose escalation study (ClinicalTrials.gov identifier: NCT06471673) in metastatic recurrent breast cancer. Bria-OTS™ represents a personalized, next generation, advancement of BriaCell’s lead candidate Bria-IMT™ which is currently in a pivotal Phase 3 study for metastatic breast cancer.

On April 24, 2025, BriaCell Confirmed 100% Resolution of Lung Metastasis with Bria-OTS. Complete resolution of lung metastasis confirmed at 4 months follow-up in a hormone receptor positive (HR+) breast cancer patient. Treatment well-tolerated and the patient remained on study with stable disease elsewhere. Sustained clinical response supports Bria-OTS personalized, off-the-shelf immunotherapy approach in Phase 1/2a metastatic breast cancer study.

On May 27, 2025, BriaCell announced that the Bria-OTS Phase 1/2 Study cleared safety evaluation, and BriaCell dosed its first patient in Bria-OTS combination with an immune checkpoint inhibitor. Specifically, Bria-OTS has cleared its safety evaluation in the Phase 1/2 study monotherapy dosage setting. Phase 1/2 study has now transitioned to dosing patients in combination with checkpoint inhibitor in metastatic breast cancer. The first Bria-OTS monotherapy patient remains on study with confirmed resolution of lung metastasis.

On June 2, 2025, BriaCell presented a poster on clinical data from Bria-OTS™ study in metastatic breast cancer (MBC).

Poster Title: Trial in progress: A study of Bria-OTS™ cellular immunotherapy in metastatic recurrent breast cancer

Session Date and Time: June 2, 2025 9:00 AM-12:00 PM CDT

**Abstract Number for Publication:**TPS1136

**Poster Board Number:**107a

**Session Type and Title:**Poster Session – Breast Cancer—Metastatic

In a dose-escalation Phase 1/2 study, heavily pre-treated MBC patients received Bria-OTS monotherapy (single agent Bria-OTS cells only). The Phase 1 segment enrolled and treated 3 patients with the first patient achieving aconfirmed resolution of a breast cancer lung metastasis and remaining on study with single agent Bria-OTS. Following successful completion of safety evaluations, BriaCell hasinitiated the combination cohort dosing the first patient with Bria-OTS plus checkpoint inhibitor (CPI).

On July 9, 2025, BriaCell announced that its patient achieved sustained complete resolution of lung metastasis in Bria-OTS™ metastatic breast cancer study. [IMAGES BELOW] shows complete resolution maintained at 6 months in first patient treated with BriaCell’s Bria-OTS in Phase 1/2a study. No treatment limited toxicities were observed. The patient remained on study with stable disease elsewhere.

BriaCell Phase 1/2 Study of Bria-OTS™, also known as Bria-BRES™, in metastatic breast cancer is ongoing.

Figure 1: Treatment with Bria-OTS monotherapy resulted in 100% resolution of tumor in the right lung of the metastatic breast cancer (MBC) patient following 2 months of therapy and confirmed at 4, and 6 months of therapy 1(axial and coronal views)

Bria-PROS+™ and Bria-BRES+™

The Company made important strides in advancing its next-generation candidates Bria-PROS+™ (for prostate cancer) and Bria-BRES+™ (for breast cancer). A key milestone was achieved on September 10, 2024, when BriaCell reported a successful Pre-IND meeting with the FDA for Bria-PROS+. In this meeting, the FDA waived requirements for animal toxicology and pharmacokinetic studies prior to opening the IND, greatly simplifying the development pathway and accelerating the clinical timeline. These regulatory concessions highlight the potential impact of Bria-PROS+ and strengthen its prospects as a first-in-class therapy.

On November 8, 2024, the Company also disclosed preclinical data for both Bria-PROS+ and Bria-BRES+, showing in vitro anti-cancer activity in breast and prostate cancer models. These findings were presented at the SITC Annual Meeting in Houston, Texas, and provided an important proof-of-concept for the scientific community. Together, these updates illustrate the breadth of BriaCell’s pipeline beyond its lead Bria-IMT program.

BriaPro Therapeutics and Antibody Development

On April 10, 2025, BriaPro Therapeutics Corp., a majority-owned subsidiary of BriaCell, announced a new initiative in antibody therapeutics. The subsidiary is developing high-affinity antibodies directed against B7-H3, an immune checkpoint molecule implicated in cancer progression and expressed on many tumor types. This initiative leverages molecular modeling techniques and is backed by provisional U.S. patent filings, with international filings under the Patent Cooperation Treaty anticipated. The antibodies are expected to be incorporated into the proprietary Bria-TILsRx™ platform, which is designed to activate tumor-infiltrating lymphocytes within the tumor microenvironment.

On July 29, 2025, BriaCell’s Subsidiary, BriaPro, filed patent application for immuno-oncology platform with novel multitargeting agents. TILsRx platform is designed to overcome immune suppression and T cell exhaustion to activate tumor-infiltrating lymphocytes (TILs). Multivalent technology enables simultaneous engagement of multiple cancer-associated and immune pathway targets. A preferred tolerability profile is expected due to selective cancer cell targeting within the tumor microenvironment (TME). TILsRx platform early agents include antibodies to B7-H3, an immune checkpoint found in several cancers including prostate, lung, breast, pancreatic, and ovarian. The platform integrates T cell engagers and immune checkpoint modulators, with the goal of both enhancing anti-tumor immune responses and selectively blocking inhibitory signals that often suppress T cell activity. This program represents a diversification of BriaCell’s pipeline into next-generation antibody modalities and underscores the Company’s leadership in immuno-oncology innovation.

License Agreements

On August 4, 2022, BriaCell announced that it has secured an exclusive license from University of Maryland, Baltimore County (UMBC) to develop and commercialize Soluble CD80 (sCD80) as a biologic agent for the treatment of cancer. Under the terms of the agreement, BriaCell has the worldwide rights to develop and commercialize sCD80, while UMBC maintains ownership of the patents (the “UMBC Licensing Agreement”). BriaCell will pay royalties to UMBC upon the commercialization of the product plus patent management costs. The licensing agreement was coordinated by UMBC’s Office of Technology Development.

Intellectual Property

The proprietary nature of, and protection for, the Company’s current and/or any future product candidates, processes and know-how are important to its business, as is its ability to operate without infringing on the proprietary rights of others, and to prevent others from infringing its proprietary rights. The Company seeks patent protection in the U.S. and internationally for its current and future product candidates it may develop through other technology. In order to protect its proprietary technologies, the Company relies on combinations of applications for patent and trade secret protection, as well as confidentiality agreements with employees, consultants, and third parties.

Bria-IMT™

Filed with the United States Patent and Trademark Office (USPTO) on June 14, 2004, U.S. Patent No. 7,674,456 B2 issued on March 9, 2010 and includes claims to the following:

1. Compositions comprising SV-BR cells; and

2. Therapeutic methods of using said compositions

The patent expires May 31, 2028 and patent term extension under Hatch-Waxman potentially applies (additional five years).

Bria-OTS™

On February 27, 2017, BriaCell™ filed an international patent application under the Patent Cooperation Treaty (PCT) to further expand its intellectual property portfolio underlying the Company’s current and anticipated pipeline of whole-cell cancer immunotherapeutics including Bria-IMT™ and Bria-OTS™. The PCT application (PCT/US2017/019757) claims priority to two provisional patent applications filed by the Company with the USPTO in 2016. It, in essence, provides the framework for additional whole-cell cancer immunotherapeutics beyond Bria-IMT™ and strategies for patient-specific selection of the most likely effective whole-cell immunotherapeutic. The PCT application entered the National Phase in the second half of 2018 and has been granted in Japan, Australia, New Zealand, and the US.

BriaCell was awarded a Japanese patent on June 21, 2021 (JP Patent No. 6901505, extends to February 27, 2037) covering composition of matter and kits for its whole-cell cancer immunotherapy technology in Japan.

BriaCell was also awarded an Australian patent on November 10, 2022 (AU Patent No. 2017224232, extends to February 27, 2037) covering composition of matter and method of use for its whole-cell cancer immunotherapy technology in Australia.

In addition, BriaCell was awarded a US patent on January 24, 2023 (US Patent No. 11,559,574 B2 with the term extending to May 25, 2040) covering composition of matter and method of use of its personalized off-the-shelf cell-based immunotherapy for cancer.

Furthermore, BriaCell was awarded a New Zealand patent on October 3, 2023 (NZ Patent No. 745327, extends to February 27, 2037) covering composition of matter, method of use, and kits for its whole-cell cancer immunotherapy technology in New Zealand.

BriaCell was awarded another New Zealand patent on June 4, 2025 (NZ Patent No. 785587, extends to February 27, 2037) covering methods of patient-specific selection of the most likely effective whole-cell cancer immunotherapy based on HLA allele profile matching.

On March 2, 2023, BriaCell filed an international patent application under the PCT to further expand its intellectual property portfolio underlying the Company’s development of innovative immunotherapeutic strategies for the treatment of advanced solid tumors including Bria-OTS™ that has been engineered to express co-stimulatory molecules and immunomodulatory cytokines. The PCT application (PCT/US2023/014337) published on September 7, 2023 as International Publication No. WO 2023/167973 A1. The PCT application entered the National Phase in the second half of 2024.

On March 29, 2024, BriaCell and the National Cancer Institute (NCI) filed an international patent application under the PCT directed to engineered mammalian dendritic cells that express exogenous MHC class II alleles for the development of innovative dendritic cell-based immunotherapeutic strategies.

Soluble CD80

The patents held under UMBC Licensing Agreement are as follows:

USPN 8,956,619 B2

USPN 9,650,429 B2

USPN 10,377,810 B2

Employees

As of the date of this filing, we had twenty-two full-time employees, located in various US states including: NY, FL, PA, SC, NV and NJ. We also have international employees located in Canada and Israel.

For the year ended July 31, 2025, the average number of employees was twenty, of whom four were executive management.

Research and Development Activities and Costs

For information regarding our clinical studies, please see above under the caption “Description of the Business - Clinical Trials.”

For the years ended July 31, 2025 and 2024, we incurred $21,150,628 and $26,442,821, respectively, of net research and development expenses (excluding share based compensation allocated to research and development employees)

Property, Plant and Equipment

The Company does not own any real property. BriaCell’s corporate offices in Canada are located at Suite 300, Bellevue Centre, 235-15 th Street, West Vancouver, BC V7T 2XI, and its corporate and research offices in the United States are located at 2929 Arch Street 3 rd Floor, Philadelphia, PA 19104.

We consider our current office and laboratory space sufficient to meet our anticipated needs for the foreseeable future and suitable for the conduct of our business.

During the year ended July 31, 2025, we purchased certain laboratory equipment in the gross amount of $ nil.

Government Regulation

The FDA and other regulatory authorities at federal, state, and local levels, as well as in foreign countries, extensively regulate, among other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring, and post-approval reporting of biologics such as those we are developing. Along with third-party contractors, we will be required to navigate the various preclinical, clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies or seek approval or licensure of our current or future product candidates. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local, and foreign statutes and regulations require the expenditure of substantial time and financial resources. A company can make only those claims relating to safety and efficacy, purity and potency that are approved by the FDA and in accordance with the provisions of the approved label.

The process required by the FDA before biologic product candidates may be marketed in the United States generally involves the following:

The testing and approval process requires substantial time, effort and financial resources, and we cannot be certain that any approvals for our current or future product candidates will be granted on a timely basis, if at all. Prior to beginning the first clinical trial with a product candidate, we must submit an IND to the FDA. An IND is a request for authorization from the FDA to administer an investigational new drug to humans. The central focus of an IND submission is on the general investigational plan and the protocol(s) for clinical studies. The IND also includes results of animal andin vitrostudies assessing the toxicology, pharmacokinetics, pharmacology, and pharmacodynamic characteristics of the product; chemistry, manufacturing, and controls information; and any available human data or literature to support the use of the investigational product. An IND must become effective before human clinical trials may begin. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises safety concerns or questions about the proposed clinical trial. In such a case, the IND may be placed on clinical hold and the IND sponsor and the FDA must resolve any outstanding concerns or questions before the clinical trial can begin. Submission of an IND therefore may or may not result in FDA authorization to begin a clinical trial.

1 Note that the FDA has waived the requirement for animal studies as Bria-IMT™, Bria-BRES™ and Bria-PROS+™ are human cellular vaccines and data from animal studies would be uninterpretable.

Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCP, which include the requirement that all research subjects provide their informed consent for their participation in any clinical trial. Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. A separate submission to the existing IND must be made for each successive clinical trial conducted during product development and for any subsequent protocol amendments. Furthermore, an IRB for each site proposing to conduct the clinical trial must review and approve the plan for any clinical trial and its informed consent form before the clinical trial begins at that site and must monitor the clinical trial until completed. Regulatory authorities, the IRB or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the subjects are being exposed to an unacceptable health risk or that the trial is unlikely to meet its stated objectives. Some studies also include oversight by a Data & Safety Monitoring Board (“DSMB”) organized by the clinical trial sponsor, which provides authorization for whether or not a clinical trial may move forward at designated check points based on access to certain data from the clinical trial, and may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects, or based on other grounds, such as no demonstration of efficacy. There are also requirements governing the reporting of ongoing clinical studies and clinical trial results to public registries.

For purposes of BLA approval, human clinical trials are typically conducted in three sequential phases that may overlap.

Phase 1, Phase 2 and Phase 3 testing may not be completed successfully within a specified period, if at all, and there can be no assurance that the data collected will support FDA approval or licensure of the product. Concurrent with clinical trials, companies may complete additional animal studies and develop additional information about the biological characteristics of the product candidate and must finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things, must develop methods for testing the identity, strength, quality and purity of the final product, or for biologics, the safety, purity and potency. Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

BLA Submission and Review by the FDA

Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development, nonclinical studies and clinical trials are submitted to the FDA as part of a BLA requesting approval to market the product for one or more indications. The BLA must include all relevant data available from pertinent preclinical and clinical studies, including negative or ambiguous results as well as positive findings, together with detailed information relating to the product’s chemistry, manufacturing, controls, and proposed labeling, among other things. Data can come from company-sponsored clinical studies intended to test the safety and effectiveness of a use of the product, or from a number of alternative sources, including studies initiated by investigators. The submission of a BLA requires payment of a substantial user fee to FDA, and the sponsor of an approved BLA is also subject to annual product and establishment user fees. These fees are typically increased annually. A waiver of user fees may be obtained under certain limited circumstances.

Once a BLA has been submitted, the FDA’s goal is to review the application within ten months after it accepts the application for filing, or, if the application relates to an unmet medical need in a serious or life-threatening indication, six months after the FDA accepts the application for filing. The review process is often significantly extended by FDA requests for additional information or clarification. The FDA reviews a BLA to determine, among other things, whether a product is safe, pure and potent and whether the facility in which it is manufactured, processed, packed, or held meets standards designed to assure the product’s continued safety, purity and potency. The FDA may convene an advisory committee to provide clinical insight on application review questions. Before approving a BLA, the FDA will typically inspect the facility or facilities where the product is manufactured. The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. Additionally, before approving a BLA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP. If the FDA determines that the application, manufacturing process or manufacturing facilities are not acceptable, it will outline the deficiencies in the submission and often will request additional testing or information. Notwithstanding the submission of any requested additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.

The testing and approval process requires substantial time, effort and financial resources, and each may take several years to complete. The FDA may not grant approval on a timely basis, or at all, and we may encounter difficulties or unanticipated costs in our efforts to secure necessary governmental approvals, which could delay or preclude us from marketing our products. After the FDA evaluates a BLA and conducts inspections of manufacturing facilities where the investigational product and/or drug substance will be produced, the FDA may issue an approval letter or a Complete Response Letter. An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications. A Complete Response Letter indicates that the review cycle of the application is complete and the application is not ready for approval. A Complete Response Letter may request additional information or clarification. The FDA may delay or refuse approval of a BLA if applicable regulatory criteria are not satisfied, require additional testing or information and/or require post-marketing testing and surveillance to monitor safety or efficacy of a product.

If regulatory approval of a product is granted, such approval may entail limitations on the indicated uses for which such product may be marketed. For example, the FDA may approve the BLA with a Risk Evaluation and Mitigation Strategy plan to mitigate risks, which could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. The FDA also may condition approval on, among other things, changes to proposed labeling or the development of adequate controls and specifications. Once approved, the FDA may withdraw the product approval if compliance with pre- and post-marketing regulatory standards is not maintained or if problems occur after the product reaches the marketplace. The FDA may require one or more Phase 4 post-market studies and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization and may limit further marketing of the product based on the results of these post-marketing studies. In addition, new government requirements, including those resulting from new legislation, may be established, or the FDA’s policies may change, which could delay or prevent regulatory approval of our products under development.

A sponsor may seek approval of its product candidate under programs designed to accelerate FDA’s review and approval of new drugs and biological products that meet certain criteria. Specifically, new drugs and biological products are eligible for Fast Track designation if they are intended to treat a serious or life-threatening condition and demonstrate the potential to address unmet medical needs for the condition. For a product candidate with Fast Track designation, the FDA may consider sections of the BLA for review on a rolling basis before the complete application is submitted if relevant criteria are met. A Fast Track designated product candidate may also qualify for priority review, under which the FDA sets the target date for FDA action on the BLA at six months after the FDA accepts the application for filing. Priority review is granted when there is evidence that the proposed product would be a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of a serious condition. If criteria are not met for priority review, the application is subject to the standard FDA review period of 10 months after FDA accepts the application for filing. Priority review designation does not change the scientific/medical standard for approval or the quality of evidence necessary to support approval.

Under the Accelerated Approval program, the FDA may approve a BLA on the basis of either a surrogate endpoint that is reasonably likely to predict clinical benefit, or a clinical endpoint that can be measured earlier than irreversible morbidity or mortality and that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments. Post-marketing studies or completion of ongoing studies after marketing approval are generally required to verify the biologic’s clinical benefit in relationship to the surrogate endpoint or ultimate outcome in relationship to the clinical benefit.

In addition, a sponsor may seek FDA designation of its product candidate as a Breakthrough Therapy, if the product candidate is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the therapy may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. If the FDA designates a breakthrough therapy, it may take actions appropriate to expedite the development and review of the application. Breakthrough designation also allows the sponsor to file sections of the BLA for review on a rolling basis.

Fast Track, Priority Review and Breakthrough Therapy designations do not change the standards for approval but may expedite the development or approval process.

Other Healthcare Laws and Compliance Requirements

Our sales, promotion, medical education and other activities following product approval will be subject to regulation by numerous regulatory and law enforcement authorities in the United States in addition to the FDA, including potentially the Federal Trade Commission, the Department of Justice, the Centers for Medicare and Medicaid Services, other divisions of the Department of Health and Human Services, and state and local governments. Our promotional and scientific/educational programs must comply with the federal Anti-Kickback Statute, the Foreign Corrupt Practices Act, the False Claims Act (“FCA”), the Veterans Health Care Act, physician payment transparency laws, privacy laws, security laws, and additional state laws similar to the foregoing.

The federal Anti-Kickback Statute prohibits, among other things, the offer, receipt, or payment of remuneration in exchange for or to induce the referral of patients or the use of products or services that would be paid for in whole or part by Medicare, Medicaid or other federal health care programs. Remuneration has been broadly defined to include anything of value, including cash, improper discounts, and free or reduced price items and services. The government has enforced the Anti-Kickback Statute to reach large settlements with healthcare companies based on sham research or consulting and other financial arrangements with physicians. Further, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a violation. In addition, the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the FCA. Many states have similar laws that apply to their state health care programs as well as private payors.

The FCA imposes liability on persons who, among other things, present or cause to be presented false or fraudulent claims for payment by a federal health care program. The FCA has been used to prosecute persons submitting claims for payment that are inaccurate or fraudulent, that are for services not provided as claimed, or for services that are not medically necessary. Actions under the FCA may be brought by the Attorney General or as a qui tam action by a private individual in the name of the government. Violations of the FCA can result in significant monetary penalties and treble damages. For example, the federal government is using the FCA, and the accompanying threat of significant liability, in its investigation and prosecution of pharmaceutical and biotechnology companies throughout the country, in connection with the promotion of products for unapproved uses and other sales and marketing practices. The government has obtained multi-million and multibillion dollar settlements under the FCA in addition to individual criminal convictions under applicable criminal statutes. In addition, companies have been forced to implement extensive corrective action plans, and have often become subject to consent decrees or corporate integrity agreements, restricting the manner in which they conduct their business. The federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) also created federal criminal statutes that prohibit, among other things, knowingly and willfully executing a scheme to defraud any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services. Given the significant size of actual and potential settlements, it is expected that the government will continue to devote substantial resources to investigating healthcare providers’ and manufacturers’ compliance with applicable fraud and abuse laws.

In addition, there has been a recent trend of increased federal and state regulation of payments made to physicians and other healthcare providers. The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act (collectively, the “Affordable Care Act”), among other things, imposed new reporting requirements on drug manufacturers for payments or other transfers of value made by them to physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members. Failure to submit required information may result in civil monetary penalties**.**Certain states also mandate implementation of commercial compliance programs, impose restrictions on drug manufacturer marketing practices and/or require the tracking and reporting of gifts, compensation and other remuneration to physicians and other healthcare professionals.

We may also be subject to data privacy and security regulation by both the federal government and the states in which we conduct our business. HIPAA, as amended by the Health Information Technology and Clinical Health Act (“HITECH”) and their respective implementing regulations, imposes specified requirements relating to the privacy, security and transmission of individually identifiable health information. Among other things, HITECH makes HIPAA’s privacy and security standards directly applicable to “business associates,” defined as independent contractors or agents of covered entities that create, receive, maintain or transmit protected health information in connection with providing a service for or on behalf of a covered entity. HITECH also increases the civil and criminal penalties that may be imposed against covered entities, business associates and possibly other persons, and gives state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorney’s fees and costs associated with pursuing federal civil actions. In addition, state laws govern the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect.

If our operations are found to be in violation of any of such laws or any other governmental regulations that apply to it, we may be subject to penalties, including, without limitation, civil and criminal penalties, damages, fines, the curtailment or restructuring of our operations, exclusion from participation in federal and state healthcare programs and imprisonment, any of which could adversely affect our ability to operate our business and our financial results. Also, the U.S. Foreign Corrupt Practices Act and similar worldwide anti-bribery laws generally prohibit companies and their intermediaries from making improper payments to foreign officials for the purpose of obtaining or retaining business. We cannot assure you that our internal control policies and procedures will protect us from reckless or negligent acts committed by our employees, future distributors, partners, collaborators or agents. Violations of these laws, or allegations of such violations, could result in fines, penalties or prosecution and have a negative impact on our business, results of operations and reputation.

Coverage and Reimbursement

Sales of pharmaceutical products depend significantly on the availability of third-party coverage and reimbursement. Third-party payors include government health administrative authorities, managed care providers, private health insurers and other organizations. Although we currently believe that third-party payors will provide coverage and reimbursement for our product candidates, if approved, these third-party payors are increasingly challenging the price and examining the cost-effectiveness of medical products and services. In addition, significant uncertainty exists as to the reimbursement status of newly approved healthcare products. We may need to conduct expensive clinical studies to demonstrate the comparative cost-effectiveness of our product candidates. Seeking coverage and reimbursement from third-party payors can be time consuming and expensive. Moreover, a payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved. Reimbursement may not be available or sufficient to allow us to sell our products on a competitive and profitable basis.

Foreign Regulation

In addition to regulations in the United States, we are and will be subject, either directly or through our distribution partners, to a variety of regulations in other jurisdictions governing, among other things, clinical trials and commercial sales and distribution of our products, if approved.

Whether or not we obtain FDA approval for a product, we must obtain the requisite approvals from regulatory authorities in non-U.S. countries prior to the commencement of clinical trials or marketing of the product in those countries. Certain countries outside of the United States have processes that require the submission of a clinical trial application much like an IND prior to the commencement of human clinical trials. In Europe, for example, a clinical trial application (“CTA”) must be submitted to the competent national health authority and to independent ethics committees in each country in which a company plans to conduct clinical trials. Once the CTA is approved in accordance with a country’s requirements, clinical trials may proceed in that country.

The requirements and process governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country, even though there is already some degree of legal harmonization in the European Union (the “E.U.”) member states resulting from the national implementation of underlying E.U. legislation. In all cases, the clinical trials are conducted in accordance with GCP and other applicable regulatory requirements.

To obtain regulatory approval of a new drug or medicinal product in the E.U., a sponsor must obtain approval of a marketing authorization application. The way in which a medicinal product can be approved in the E.U. depends on the nature of the medicinal product.

The centralized procedure results in a single marketing authorization granted by the European Commission that is valid across the E.U., as well as in Iceland, Liechtenstein and Norway. The centralized procedure is compulsory for human drugs that are: (i) derived from biotechnology processes, such as genetic engineering, (ii) contain a new active substance indicated for the treatment of certain diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative diseases, autoimmune and other immune dysfunctions and viral diseases, (iii) officially designated as “orphan drugs” and (iv) advanced-therapy medicines, such as gene-therapy, somatic cell-therapy or tissue-engineered medicines. The centralized procedure may at the request of the applicant also be used for human drugs which do not fall within the above mentioned categories if the human drug (a) contains a new active substance which was not authorized in the European Community; or (b) the applicant shows that the medicinal product constitutes a significant therapeutic, scientific or technical innovation or that the granting of authorization in the centralized procedure is in the interests of patients or animal health at the European Community level.

Under the centralized procedure in the E.U., the maximum timeframe for the evaluation of a marketing authorization application by the EMA is 210 days (excluding clock stops, when additional written or oral information is to be provided by the applicant in response to questions asked by the Committee for Medicinal Products for Human Use (“CHMP”)), with adoption of the actual marketing authorization by the European Commission thereafter. Accelerated evaluation might be granted by the CHMP in exceptional cases, when a medicinal product is expected to be of a major public health interest from the point of view of therapeutic innovation, defined by three cumulative criteria: (i) the seriousness of the disease to be treated, (ii) the absence of an appropriate alternative therapeutic approach, and (iii) anticipation of exceptional high therapeutic benefit. In this circumstance, EMA ensures that the evaluation for the opinion of the CHMP is completed within 150 days and the opinion issued thereafter.

The Mutual Recognition Procedure (“MRP”) for the approval of human drugs is an alternative approach to facilitate individual national marketing authorizations within the E.U. The MRP may be applied for all human drugs for which the centralized procedure is not obligatory. The MRP is applicable to the majority of conventional medicinal products, and is based on the principle of recognition of an already existing national marketing authorization by one or more member states.

The characteristic of the MRP is that the procedure builds on an already existing marketing authorization in a member state of the E.U. that is used as reference in order to obtain marketing authorizations in other E.U. member states. In the MRP, a marketing authorization for a drug already exists in one or more member states of the E.U. and subsequently marketing authorization applications are made in other E.U. member states by referring to the initial marketing authorization. The member state in which the marketing authorization was first granted will then act as the reference member state. The member states where the marketing authorization is subsequently applied for act as concerned member states.

The MRP is based on the principle of the mutual recognition by E.U. member states of their respective national marketing authorizations. Based on a marketing authorization in the reference member state, the applicant may apply for marketing authorizations in other member states. In such case, the reference member state shall update its existing assessment report about the drug in 90 days. After the assessment is completed, copies of the report are sent to all member states, together with the approved summary of product characteristics, labeling and package leaflet. The concerned member states then have 90 days to recognize the decision of the reference member state and the summary of product characteristics, labeling and package leaflet. National marketing authorizations shall be granted within 30 days after acknowledgement of the agreement.

Should any E.U. member state refuse to recognize the marketing authorization by the reference member state, on the grounds of potential serious risk to public health, the issue will be referred to a coordination group. Within a timeframe of 60 days, member states shall, within the coordination group, make all efforts to reach a consensus. If this fails, the procedure is submitted to an EMA scientific committee for arbitration. The opinion of this EMA Committee is then forwarded to the Commission, for the start of the decision-making process. As in the centralized procedure, this process entails consulting various European Commission Directorates General and the Standing Committee on Human Medicinal Products or Veterinary Medicinal Products, as appropriate.

For other countries outside of the E.U., such as countries in Eastern Europe, Latin America or Asia, the requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country. In all cases, again, the clinical trials are conducted in accordance with GCP and the other applicable regulatory requirements.

If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension of clinical trials, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.

Plan of Arrangement for BriaPro Therapeutics Corp.

On August 31, 2023, the Company closed a plan of arrangement spinout transaction (the “Arrangement”). Pursuant to the Arrangement, certain pipeline assets of the Company were spun-out to BriaPro Therapeutics Corp. (“BriaPro” or “SpinCo”), including Bria-TILsRx™ and protein kinase C delta (PKCδ) inhibitors for multiple indications including cancer (the “BriaPro Assets”), resulting in a two-third (2/3) owned subsidiary of the Company with the remaining one-third (1/3) held by the Company’s shareholders. BriaPro has acquired the entire right and interest in and to the BriaPro Assets in consideration for the issuance by BriaPro to the Company of BriaPro’s common shares. Under the terms of the Arrangement, for each common share of the Company held immediately prior to closing, the shareholders of the Company received one common share of BriaPro, and one new common share of the Company (retiring their old share) having the same terms and characteristics as the existing common shares of the Company. The Company’s common shares and public warrants remained listed on the Nasdaq Capital Market and the common shares remained listed on the Toronto Stock Exchange, and SpinCo is an unlisted reporting issuer in Canada. As part of the Arrangement, the Company obtained a third-party independent valuation for BriaPro which amounted to $1.75 million. Based on the number of issued shares of BriaPro, this amounts to $0.0365 per BriaPro share.

BriaPro is a pre-clinical stage immunotherapy company developing binding agents and proteins with the intention to boost the ability of the body’s own cancer-fighting cells to destroy cancerous tumors. Using artificial intelligence (“AI”) with ImmunoPrecise Antibodies and Receptor AI, BriaPro will identify drug candidates.

The lead drug discovery candidates for BriaPro includes:

The power of AI in drug candidate selection has been hailed by experts and investments in AI-driven drug discovery companies have tripled over the past four years, reaching $24.6 billion in 2022.2 Using AI technology to identify the next blockbuster therapies can help eliminate some of the guesswork that typically requires hundreds of lab experiments-often spread over many years-to identify promising molecules.

Instead of coming up with tens of thousands of compounds to figure out, computers suggest testing ten compounds in a lab, then getting feedback from the lab results. The machines learn from those results to make a better prediction to provide the next hundred candidates for testing and ultimately filter to one molecule.

Over the course of the next year, BriaPro expects to screen several different multi specific binding reagents for activity in vitro as well as in mouse models of cancer. BriaPro also expects to select at least one candidate to advance into IND enabling studies. Human clinical studies are expected to be initiated in the first half of 2025. In parallel, BriaPro will continue to optimize the structure of its proprietary protein kinase C delta inhibitors and advance to the candidates election stage. Human clinical studies are expected to be initiated in the second half of 2025.

Financings and share consolidations Summary

During the fiscal year ended July 31, 2025, BriaCell completed several financings, raising a total of approximately $50.9 million in gross proceeds before deducting fees and expenses. These transactions significantly bolstered the Company’s capital position, enhancing its ability to fund ongoing clinical trials, advance its pipeline programs, and support operational needs. The financings also demonstrates continued investor confidence in BriaCell’s immunotherapy platforms and clinical progress.

On January 27, 2025, the Company issued a press release announcing the consolidation of the issued and outstanding common shares of the Company on the basis of one (1) post-consolidation common share for every fifteen (15) pre-consolidation common shares became effective under the corporate law of British Columbia, Canada on January 24, 2025. The post-consolidation common shares commenced trading on the Toronto Stock Exchange and the Nasdaq Capital Market at market open on January 29, 2025, under new CUSIP number 107930208.

On August 21, 2025, the Company issued a press release announcing the consolidation of the issued and outstanding common shares of the Company on the basis of one (1) post-Consolidation common share for every ten (10) pre-consolidation common shares which became effective under the corporate law of British Columbia, Canada on August 25, 2025. The post-Consolidation common shares commenced trading on the Toronto Stock Exchange and The Nasdaq Capital Market at market open on August 25, 2025, under the new CUSIP number 107930307.