What changed in this filing

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Item 1. Business

2023-10-25 compared with 2022-10-28 · 550 added, 925 removed, 838 unchanged (64% of the section changed)

of the Company

(the “ Company ”) is an immuno-oncology biotechnology company with a strong focus on cancer immunotherapy.

Immunotherapies have come to the forefront in the fight against cancer since they harness the body’s own immune system to recognize

and destroy cancer cells.

BriaCell owns the U.S.

patent to SV-BR-1-GM (“ Bria-IMT™ ”), a whole-cell targeted immunotherapy

for cancer (U.S.

7,674,456), as well as patents related to PKCδ inhibitors (U.S.

9,364,460 and 9,572,793).

The Company is currently advancing our targeted immunotherapy program by prioritizing a Phase I/IIa clinical trial with Bria-IMT™

in combination with an immune checkpoint inhibitor and a companion diagnostic test, BriaDx™, to identify patients most likely to

benefit from Bria-IMT™.

The Bria-IMT™ regimen was evaluated in four patients in a prior study in 2004-2006 by Dr.

Wiseman, the scientific founder, former member of the board of directors of the Company (the “ Board ”) and principal

scientific advisor.

Encouraging results were obtained, especially in a patient who matched Bria-IMT™ at HLA-DR alleles and had

a grade II tumor.

In 2017-2018 BriaCell evaluated 23 patients with advanced breast cancer with the Bria-IMT™ regimen and obtained

confirmation of the ability of the Bria-IMT™ regimen to induce regression of metastatic breast cancer in patients who match Bria-IMT™

at least at one HLA allele and/or if they had grade I or grade II tumors.

A combination study with the immune checkpoint inhibitor pembrolizumab

(KEYTRUDA®) was initiated and the first patient dosing in the “combination therapy” clinical trial occurred in September

BriaCell purchased the KEYTRUDA® for this study as BriaCell does not have an agreement with Merck & Co., Inc.

for the supply

of KEYTRUDA®.

Eleven patients were dosed in the combination therapy trial with Bria-IMT™ and the immune checkpoint inhibitor

KEYTRUDA® and subsequently dosing with this combination was discontinued.

The study was modified under an amended protocol which

evaluates the combination of the Bria-IMT™ regimen with Incyte Corporation experimental drugs retifanlimab (anti-PD-1 antibody

similar to pembrolizumab).

The study is ongoing.

is estimated by the National Cancer Institute that in 2022, approximately 287,500 women will be diagnosed with breast cancer in the United

That means that every two minutes an American woman is diagnosed with breast cancer and more than 43,000 are projected to die

Therapeutics Corp.

(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 in a pivotal 1 Phase 3 study in advanced metastatic breast cancer.

BriaCell recently reported

benchmark-beating patient survival and clinical benefit in advanced metastatic breast with median overall survival of 13.5 months in

BriaCell’s advanced metastatic breast cancer patients vs.

6.7-9.8 months for similar patients reported in the literature 2 .

A completed Bria-IMT™ Phase 1 combination study with retifanlimab (an anti-PD1 antibody manufactured by Incyte) confirmed tolerability

and early-stage efficacy.

BriaCell is also developing a personalized off-the-shelf immunotherapy, Bria-OTS™, which provides a platform

technology to develop personalized off-the-shelf immunotherapies for numerous types of cancer, and a soluble CD80 protein therapeutic

which acts both as a stimulator of the immune system as well as an immune checkpoint inhibitor.

is estimated by the National Cancer Institute that in 2023, approximately 297,790 women 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 43,170 are

projected to die in 2023.

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 2,710 new cases of invasive

male breast cancer will be diagnosed and approximately 530 men will die from breast cancer in 2022.

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 530 men will die from breast cancer in

to the May 2023 “Global Oncology Trends 2023” report by the IQVIA Institute, the global market for cancer drugs (including

1 unchanged sentence

of 17% between 2023 and 2027, of which about 20% is expected to be immuno-oncology drugs.

About 12.9% percent of women will be diagnosed

with breast cancer at some point during their lifetime.

In 2018, there were an estimated 3,676,262 women living with female breast cancer

in the United States.

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

of a treatment.

Cortes J, et al.

Annals of Oncology 2018;

Kazmi S, et al.

Breast Cancer Res Treat.

O’Shaughnessy J et al.

Cancer Res Treat.

Tripathy D, et al.

About 13% percent

of women will be diagnosed with breast cancer at some point during their lifetime.

In 2022, 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.

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

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is estimated that over 150,000 women in the US are living with MBC.

2 For those with metastatic disease at diagnosis, their

5-year survival rate is 27%.

3 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 failed at least two lines of therapy.

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.

See https://seer.cancer.gov/statfacts/html/breast.html

2 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.

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.

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.

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

Mariotto AB, Etzioni R, Hurlbert M, Penberthy L, Mayer M.

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These precedents demonstrate a strong market pull for Bria-IMT™.

2018 Sales US

2018 Sales Ex-US

2018 Sales WW

HERCEPTIN® (trastuzumab)

Monoclonal antibody

HER2+BC & HER2+ metastatic gastric cancer

IBRANCE® (palbociclib) in combination with fluvestrant or aromatase inhibitor

CDK 4/6 inhibitor

HR+/HER2- MBC

PERJETA® (pertuzumab) in combination with Herceptin® (trastuzumab) and chemotherapy

HER2/neu receptor antagonist

HER2+ early BC that has a high likelihood of recurrence

FASLODEX® (fulvestrant)

Estrogen receptor antagonist

HR+/HER2- MBC

KADCYLA® (ado-trastuzumab emtansine)

HER2 targeted antibody & microtubule inhibitor conjugate

LYNPARZA® (olaparib)

Poly (ADP-ribose) polymerase (PARP) inhibitor

BC & Ovarian cancer

Verzenio® (abemaciclib) monotherapy or in combination with fulvestrant or aromatase inhibitor

CDK 4/6 inhibitor

HR+/HER2- MBC

KISQALI® (ribociclib) in combination with fluvestrant or aromatase inhibitor

CDK 4/6 inhibitor

HR+/HER2- MBC

best response to Bria-IMT™ to date is in patients who matched Bria-IMT™ at one or more HLA alleles, with higher response

rates for patients with 2+ HLA allele matches.

If one HLA allele match is found to be sufficient, we will be able to treat ~50-60% of

the patient population, while patients with 2+ HLA matches constitutes ~15-35% of cases.

8 We also saw higher clinical benefit

rates for patients with grade I/II tumors.

Tumor differentiation in breast cancer cell lines is often described by their classification

as Luminal, Basal A and Basal B subtypes, with Luminal representing well differentiated tumors, Basal B poorly differentiated tumors,

and Basal A an intermediate stage tumor (“moderately” differentiated).

Yao and colleagues in 2005 identified a 9-gene signature (AURKB, CENPI, DEPDC1, DEPDC1B, FAM83D, FGD3, NCAPH, TNFRSF18, FCGR1A)

discriminating poorly (grade 3) from moderately (grade 2) differentiated tumors.

To understand the place of SV-BR-1-GM in this model, we compared its RNA expression profile with those of three other cell lines

representing Luminal (MCF-7), Basal A (MDA-MB-468) and Basal B (MDA-MB-231), using a 10-gene signature (AURKB, CENPI, DEPDC1, DEPDC1B,

FAM83D, FGD3, NCAPH, DLGAP, KIF2C, VAV3) derived from those by Yao and colleagues.

The results, shown in the figure below, demonstrate

that Bria-IMT™ most closely clusters with MDA-MB-468 and as such is considered a grade II “moderately differentiated”

best response to the Bria-IMT™ monotherapy regimen to date is in patients who matched Bria-IMT™ at one or more HLA

alleles, with higher response rates for patients with 2+ HLA allele matches.

If one HLA allele match is found to be sufficient, we

will be able to treat ~50-60% of the patient population, while patients with 2+ HLA matches constitutes ~15-35% of

8 We also saw higher clinical benefit rates for patients with grade I/II tumors.

Tumor differentiation in breast

cancer cell lines is often described by their classification as Luminal, Basal A and Basal B subtypes, with Luminal representing

well differentiated tumors, Basal B poorly differentiated tumors, and Basal A an intermediate stage tumor (“moderately”

differentiated).

2 Yao and colleagues in 2005 identified a 9-gene signature (AURKB, CENPI, DEPDC1, DEPDC1B, FAM83D, FGD3,

NCAPH, TNFRSF18, FCGR1A) discriminating poorly (grade 3) from moderately (grade 2) differentiated tumors.

3 To understand

the place of SV-BR-1-GM in this model, we compared its RNA expression profile with those of three other cell lines representing

Luminal (MCF-7), Basal A (MDA-MB-468) and Basal B (MDA-MB-231), using a 10-gene signature (AURKB, CENPI, DEPDC1, DEPDC1B, FAM83D,

FGD3, NCAPH, DLGAP, KIF2C, VAV3) derived from those by Yao and colleagues.

The results, shown in the figure below, demonstrate that

Bria-IMT™ most closely clusters with MDA-MB-468 and as such is considered a grade II “moderately differentiated”

Results from the EMERGE multicenter retrospective chart review study.

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Neve RM, Chin K, Fridlyand J, et al.

A collection of breast cancer cell lines for the study of functionally distinct

cancer subtypes.

A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes.

2006;10(6):515-527.

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Yao F, Zhang C, Du W, Liu C, Xu Y.

Identification of gene-expression signatures and protein markers for breast cancer

grading and staging.

Identification of gene-expression signatures and protein markers for breast cancer grading and

Doi:10.1371/journal.pone.0138213)

on a recent publication of patients with relapsed breast cancer, we estimate that this will account for ~40% of relapsed metastatic breast

on a publication of patients with relapsed breast cancer, we estimate that this will account for ~40% of relapsed metastatic breast

cancer cases (33% grade II and 7% grade I) (Sundquist M, Brudin L, Tejler G.

5 unchanged sentences

following relapse appears similar for those with grade II and grade III tumors.

recent information comes from combination therapy studies of the Bria-IMT™ regimen with immune checkpoint inhibitors (CPI).

the ongoing study of BRI-ROL-001, in phase I the Bria-IMT™ regimen was dosed in combination with Keytruda ® in 11 patients

and in 12 patients with Zynyz® with one patient starting on the combination with Keytruda® and crossing-over to the combination

with Zynyz® (22 patients total).

In phase II of the study, the Bria-IMT™ regimen is being dosed in combination with Zynyz®

with patients randomized to either receive the Bria-IMT™ regimen first (12 patients) or Zynyz® first (12 patients).

11 patients treated in combination with Keytruda® in phase I, the disease control data is shown below:

patients were treated with Bria-IMT™ + Keytruda®

patients were very heavily pre-treated with a median of 7 prior systemic therapy regimens

chemotherapy), further underscoring BriaCell’s positive patient outcomes

■ Tolerability

excellent with no dose-limiting toxicities

benefit demonstrated:

1 PR and 3 SD in 8 immune responders

the 12 patients treated in combination with Zynyz® in phase I, the disease control data is shown below:

patients were treated with Bria-IMT™ plus Zynyz®

patients were very heavily pre-treated with a median of 5 prior systemic therapy regimens

chemotherapy), further underscoring BriaCell’s positive patient outcomes

■ Tolerability

excellent with no dose-limiting toxicities

70% (7/10) of evaluable patients showed disease control (5/10 evaluable patients including

1 PR and 4 SD) and/or progression-free survival (PFS) benefits compared with their last therapy

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 advanced breast cancer who have failed at least 2 prior regimens.

Several recent publications are noted here:

Annals of Oncology 2018:

Open-label randomized phase 3 trial

Median 4 prior lines of Rx;

~20% HER2 positive, ~20%TNBC;

n= 298 vs 296 (vinflunine vs alkylating

Response Rate (ORR) 6% vs 4%;

Clinical Benefit Rate (CBR) 44% vs 35%;

Progression Free Survival

(PFS) 1.9 vs 2.5 months;

Overall Survival (OS) 9.3.

vs 9.1 months

Breast Cancer Res Treat.

Overall survival analysis

2 prior lines of Rx;

229 Rx w eribulin, 134 gemcitabine, 80 capecitabine;

29% TNBC, 62% HR+/HER2-,

OS eribulin 9.8 months, gemcitabine 7.2 months, capecitabine 9.1 months

■ O’Shaughnessy

Breast Cancer Res Treat.

Phase 3 randomized ASCENT study

4-5 prior lines of Rx;

235 on Sacituzumab, 233 on TPC;

31% non-TNBC initially, 69% TNBC at

w/o initial TNBC:

ORR 31% vs 4% ;

CBR 44% vs 7%;

PFS 4.6 vs 2.3 months;

OS 12.4 vs 6.7 months

w initial TNBC:

ORR 36% vs 5%;

CBR 45% vs 10%;

PFS 5.7 vs 1.6 months;

OS 12.1 vs 6.9 months

Phase 3 ATTAIN Randomized Clinical Trial

■ Patients:~90%

≥4 prior lines of Rx;

92 on Etirinotecan Pegol 86 TPC;

~15% HER2+ ~40% TNBC

4.8% vs 2.7%;

CBR 24.1% vs 9.5%;

PFS 2.8 vs 1.9 months;

OS 7.8 vs 7.5 months

contrast, the Bria-IMT™ regimen with a CPI has shown a median overall survival (OS) of 13.3 months for patients treated before

2022 and 13.5 months for all patients by the Kaplan Meier method, as shown in the Figure below.

For patients treated since 2022, the

median OS has not been reached.

Overall Survival of Patients with Metastatic Breast Cancer treated with the Bria-IMT™ regimen with a CPI.

The market for breast cancer drugs is a multibillion-dollar

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by SV-BR-1-GM:

There are 150,000 women with

metastatic breast cancer in the U.S.

~45% will receive third line

therapy 11 = 68,000 patients available

68,000 x 50% (matched for 1

HLA allele group) 12 = 34,000 patients available for treatment 13

40% have grade I/II tumors 14

= 13,600 patients available for treatment

Cancer Incidence

cancer incidence and mortality.

IV mortality rate represents 3L+ patient mortality rate

novo incidence growth rate of 0.53% / year

0.2% Stage III:

Local relapse:

61% Stage III:

118K Stage III:

80K Stage IV:

stage Incidence Rate

US only stage III and IV patients.

Compliance Rate

research based on SOC therapy data

% Market Share

Cannibalization

Price (Yearly)

yearly price growth

annual cost of model PD-(L)1i

Gross to Net discount

See note 5, above.

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.

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.

2019 Jan 18;19(1):88.

Gragert, Loren, Abeer Madbouly, John Freeman, and Martin Maiers.

“Six-Locus High Resolution HLA Haplotype Frequencies

Derived from Mixed-Resolution DNA Typing for the Entire US Donor Registry.” Human Immunology.

Momenimovahed Z, Salehiniya H.

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American Cancer Society, Inc.

11 Liang TJ, Wang BW, Liu SI, Yeh MH, Chen

YC, Chen JS, Mok KT, Chang HT.

Recurrence after skin-sparing mastectomy and immediate transverse rectus abdominis musculocutaneous flap

reconstruction for invasive breast cancer.

World J Surg Oncol.

2013 Aug 14;11(1):194.

10.1186/1477-7819-11-194.

12 Dawood S, Broglio K, Ensor J, Hortobagyi

GN, Giordano SH.

Survival differences among women with de novo stage IV and relapsed breast cancer.

2010 Nov;21(11):2169-2174.

10.1093/annonc/mdq220.

Epub 2010 Apr 28.

13 Zhao H, Lei X, Niu J, Zhang N, Duan

Z, Chavez-MacGregor M, Giordano SH.

Prescription Patterns, Initiation, and 5-Year Adherence to Adjuvant Hormonal Therapy Among Commercially

Insured Patients With Breast Cancer.

JCO Oncol Pract.

2021 Jun;17(6):e794-e808.

10.1200/OP.20.00248.

Epub 2021 Feb 17.

See note 5, above.

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Evaluating response rates (partial and

complete responses = ORR), progression free survival (“ PFS ”) and overall survival (“ OS ”) from clinical

trials in similar subjects with metastatic or recurrent breast cancer indicate that response rates range from 6.9% up to 59%, depending

on the population studied and the intervention (median 24%).

PFS ranges from 8 weeks to 12 months (median 5 months) and OS from 6 months

to 31 months (median 13 months).

complete responses = ORR), progression free survival (“PFS”) and overall survival (“OS”) from clinical trials

in similar subjects with metastatic or recurrent breast cancer indicate that response rates range from 2.7% up to 59%, depending on the

population studied and the intervention (median 24%).

PFS ranges from 8 weeks to 12 months (median 5 months) and OS from 6 months to

31 months (median 13 months).

Studies evaluating second-line or later treatment options.

2 unchanged sentences

Treatment & Design

Paclitaxel Monotherapy

Gemcitabine Monotherapy

Vinorelbine Monotherapy

Cyclophosphamide and megestrol acetate

21 unchanged sentences

Lapatinib with trastuzumab

alkylating agent

O’Shaughnessy 28

Treatment of Physicians Choice

Etirinotecan Pegol

Treatment of Physicians Choice

treated with second or higher lines of therapy has a very poor prognosis and few effective therapies that consistently induce long-term

5 unchanged sentences

different therapeutic treatment options and drugs used upon diagnoses from biopsy and identification of breast cancer biomarkers.

A., Vogel, C.

L., Irwin, D.

H., Kirshner, J.

Multicenter Phase II Trial of Weekly Paclitaxel in Women

With Metastatic Breast Cancer.

19, 4216–4223 (2001).

Gemcitabine as single-agent therapy in the management of advanced breast cancer.

Oncology (Williston Park).

Weekly vinorelbine is an effective palliative regimen after failure with anthracyclines and taxanes in metastatic

breast carcinoma.

Cancer 92, 2267–72 (2001).

Licchetta A, Correale P, Migali C, Remondo C, Francini E, Pascucci A, Magliocca A, Guarnieri A, Savelli V, Piccolomini A, Carli

35 unchanged sentences

28, 1124–1130 (2010).

Dawood S, Broglio K, Ensor J, Hortobagyi GN, Giordano SH.

Survival differences among women with de novo stage IV and relapsed breast

21(11):2169–74;

Bonotto M, Gerratana L, Iacono D, Minisini AM, Rihawi K, Fasola G, Puglisi F.

of Metastatic Breast Cancer in a Real-World Scenario:

Is Progression-Free Survival With First Line Predictive of Benefit From Second

and Later Lines?

26 Cortes J, Perez-Garcia J, Levy C, Gómez

Pardo P, Bourgeois H, Spazzapan S, Martínez-Jañez N, Chao TC, Espié M, Nabholtz JM, Gonzàlez Farré

X, Beliakouski V, Román García J, Holgado E, Campone M.

Open-label randomised phase III trial of vinflunine versus an alkylating

agent in patients with heavily pretreated metastatic breast cancer.

2018 Apr 1;29(4):881-887.

10.1093/annonc/mdy051.

27 Kazmi S, Chatterjee D, Raju D, Hauser

R, Kaufman PA.

Overall survival analysis in patients with metastatic breast cancer and liver or lung metastases treated with eribulin,

gemcitabine, or capecitabine.

Breast Cancer Res Treat.

2020 Nov;184(2):559-565.

10.1007/s10549-020-05867-0.

Epub 2020 Aug 17.

Breast Cancer Res Treat.

2021 Jun;187(2):603.

28 O’Shaughnessy J, Brufsky A, Rugo HS,

Tolaney SM, Punie K, Sardesai S, Hamilton E, Loirat D, Traina T, Leon-Ferre R, Hurvitz SA, Kalinsky K, Bardia A, Henry S, Mayer I, Zhu

Y, Phan S, Cortés J.

Analysis of patients without and with an initial triple-negative breast cancer diagnosis in the phase 3 randomized

ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer.

Breast Cancer Res Treat.

2022 Sep;195(2):127-139.

10.1007/s10549-022-06602-7.

Epub 2022 May 11.

29 Tripathy D, Tolaney SM, Seidman AD, Anders

CK, Ibrahim N, Rugo HS, Twelves C, Dieras V, Müller V, Tagliaferri M, Hannah AL, Cortés J.

Phase III study of etirinotecan

pegol versus treatment of physician’s choice in patients with metastatic breast cancer and brain metastases.

Future Oncol.

2019 Jul;15(19):2211-2225.

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

Results from the EMERGE multicenter retrospective chart review study.

2019 Jan 18;19(1):88.

10.2217/fon-2019-0180.

Epub 2019 May 10.

Cancer Network (NCCN®).

Current treatment paradigm for metastatic breast cancer including between different treatment strategies and combination therapies

4 unchanged sentences

regulatory review of novel therapies such as Bria-IMT™.

there are approximately 36 different biotech companies working to create an effective breast cancer vaccine, a significant gap remains

there are many biotech companies working to create an effective breast cancer 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

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.

32 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.

33 An immunogen targeting a carbohydrate antigen, globo-H, was associated with

improved PFS, but only in the subset able to mount antibody responses.

34 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

32 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.

33 An immunogen targeting a carbohydrate antigen, globo-H, was associated with improved

PFS, but only in the subset able to mount antibody responses.

34 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.

38 unchanged sentences

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 ”).

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”).

Products/Pipeline

BriaCell’s lead candidate, is a whole-cell immunotherapy undergoing clinical testing in patients with MBC who have failed prior

lines of therapy.

BriaCell has been conducting a Phase I/IIa clinical trial of Bria-IMT™, in combination with immune checkpoint

inhibitors such as pembrolizumab (KEYTRUDA®;

manufactured by Merck & Co., Inc.).

The combination study is listed in ClinicalTrials.gov

as NCT03328026 under FDA-approved BB-IND 10312 under protocol BRI-ROL-001 at three clinical sites:

Joseph Heritage Healthcare in

Santa Rosa, California, United States;

University of Miami/Sylvester at Plantation, in Plantation, Florida, USA;

Cancer Center of Kansas,

in Wichita, Kansas, USA.

Subsequent to the establishment of a collaboration with Incyte Corporation, this study has been modified to

evaluate the combination of the Bria-IMT™ with retifanlimab (also referred to as INCMGA00012 ,a PD-1 inhibitor).

has achieved proof of concept based on data from a Phase I/IIa study of Bria-IMT™ in advanced breast cancer patients.

BriaCell obtained evidence that patients with certain HLA molecules also present in Bria-IMT™ have a higher likelihood of responding

to the Bria-IMT™ regimen with tumor regression (“ shrinkage ”), which is consistent with results from a molecular

analysis of Bria-IMT™ conducted by BriaCell.

BriaCell’s lead candidate, is a whole-cell immunotherapy.

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.

pivotal Phase 3 combination study is listed on ClinicalTrials.gov as NCT06072612.

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 the FDA, could lead to full approval of the Bria-IMT™ immune checkpoint inhibitor combination in advanced metastatic breast

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.

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

successful completion of the pivotal study would allow BriaCell to subsequently submit a Biologics License Application and accelerate

the path to commercialization.

recently announced partnership with New York Cancer & Blood Specialists (“NYCBS”) as clinical site with more than 30 locations and

35 hospital affiliations throughout Nassau and Suffolk counties, in the Bronx, Manhattan, Queens, Staten Island, and Brooklyn to conduct

its pivotal Phase 3 Study of Bria-IMT™ in Advanced Breast Cancer.

collaboration with Prevail InfoWorks, Inc.

(“InfoWorks”), a Philadelphia, PA based contract research organization,

BriaCell expects 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.

Partners, LLC (“Prevail Partners”), an investment fund and affiliate of InfoWorks, has purchased 463,408 BriaCell common

shares at a price of $8.63 for gross proceeds of $4 million, representing 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.

The transaction closed on May 19, 2023.

Letter of Intent from Weill Cornell Medicine Outlining Plans to Initiate a Phase 2 Clinical Trial of Bria-IMT™ in High-Risk Early-Stage

Triple Negative Breast Cancer

recently announced that it has accepted a letter of intent from Dr.

Massimo Cristofanilli, Director of Breast Medical Oncology and Associate

Director of Precision Medicine in the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, outlining the parties’ plans

and commitment, upon regulatory approval, to initiate a Phase 2 investigator-initiated clinical study to evaluate BriaCell’s novel

immunotherapy, Bria-IMT™, in combination with a check point inhibitor, in early stage, newly diagnosed, high-risk triple

negative breast cancer patients who have failed to achieve a pathological complete response in the neoadjuvant setting.

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 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 as NCT03328026 under FDA-approved BB-IND 10312 under protocol BRI-ROL-001 at ten clinical sites throughout the

United States.

recently announced benchmark-beating patient survival and clinical benefit in advanced metastatic breast cancer with median overall survival of 13.5 months in BriaCell’s advanced metastatic breast cancer patients vs.

months for similar patients reported in the literature.

has achieved proof of concept based on data from a Phase 1/2a study of Bria-IMT™ in advanced breast cancer patients.

BriaCell has demonstrated disease control and clinical benefit in a high proportion of patients with advanced breast cancer

who have exhausted other therapeutic options.

There is also promising data on overall survival as noted above.

Proof of Concept

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with 20-50 million irradiated Bria-IMT™ cells between two and three days later, with subsequent intradermal inoculation with

interferon-α2 approximately two and four days later.

interferon-α2 approximately two days later.

This is known as the Bria-IMT™ regimen.

Both were single arm studies,

so there were no untreated patients for comparison.

has evaluated the Bria-IMT™ regimen in two Phase I/IIa studies of Bria-IMT™ in advanced breast cancer patients.

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.

Both were single arm studies, so there were no untreated patients for comparison.

were four evaluable patients treated in one study (Study SVMC #01-026) and 23 evaluable patients treated in another study (Study

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a median of four prior systemic therapy regimens.

shows an outstanding safety and tolerability profile for Bria-IMT™ in advanced breast cancer patients.

SVMC #01-026 study, treatment was limited to six cycles over five months.

Four post-menopausal white women were enrolled aged between

58.7 and 73 years.

data shows an outstanding safety and tolerability profile for Bria-IMT™ in advanced breast cancer patients.

Study SVMC #01-026

the SVMC #01-026 study, treatment was limited to six cycles over five months.

Four post-menopausal white women were enrolled aged

between 58.7 and 73 years.

Three had breast cancer and one had Her2+ ovarian cancer.

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No deaths were reported during

There were four serious adverse events (“ SAEs ”) in 3 patients with one (transient urticaria, grade

3) judged probably related to treatment.

There were four serious adverse events (“SAEs”) in 3 patients with one (transient urticaria, grade 3) judged

probably related to treatment.

All SAEs were manageable with community practice therapies.

Bria-IMT™ regimen was able to elicit delayed-type hypersensitivity (“DTH”) responses in all patients.

is a measure of cell-mediated immunity.

measure of cell-mediated immunity.

This response involves the interaction of T-cells, monocytes, and macrophages.

This reaction

is caused when CD4+ Th1 helper T cells recognize foreign antigen in a complex with the Class II HLA molecule on the surface of antigen-presenting

This reaction is

caused when CD4+ Th1 helper T cells recognize foreign antigen in a complex with the Class II HLA molecule on the surface of antigen-presenting

These can be macrophages or dendritic cells that secrete monokines such as IL-12 and IL-15, which stimulates the proliferation

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of stability of bone lesions.

She completed therapy and 3 months after her last Bria-IMT™ inoculation, imaging studies identified

regrowth of tumor notably in the breast, lung, and brain.

After consultation with the FDA, the patient was treated off-protocol which

also produced tumor regression, including the resolution of brain metastases.

The HLA-DRB3 allele of patient A002 matched with that

of SV-BR-1-GM and the HLA-DRB1 allele of patient A002 also matched that of SV-BR-1-GM.

Her tumor was grade II (moderately differentiated).

One other patient on this study (B001) with a grade II tumor had disease limited to bony metastases.

She did not have measurable

disease but was felt to progress on study.

She completed therapy and 3 months after her last Bria-IMT™ inoculation, imaging studies

identified regrowth of tumor notably in the breast, lung, and brain.

After consultation with the FDA, the patient was treated

off-protocol which also produced tumor regression, including the resolution of brain metastases.

The HLA-DRB3 and HLA-DRB1 alleles

of patient A002 matched with that of SV-BR-1-GM.

was grade II (moderately differentiated).

One other patient on this study (B001) with a grade II tumor had disease limited to bony

She did not have measurable disease but was felt to progress on study.

time to tumor progression was 144 days (range 64 – 223 days) for the initial round of treatment.

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than 33 months in all patients except B001 (7 months).

WRI-GEV-007 study, patients were treated with a median of three cycles of therapy (range 1-8).

the WRI-GEV-007 study, patients were treated with a median of three cycles of therapy (range 1-8).

Bria-IMT™ regimen was able to elicit both cellular immune responses (as evidenced by DTH responses in 85% of patients evaluated)

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most common adverse events seen were local irritation at the inoculation sites.

There was one serious adverse event of gastrointestinal

reflux disease possibly related to Bria-IMT™.

patients showed evidence of anti-tumor activity of the Bria-IMT™ regimen in spite of their being heavily pre-treated advanced

breast cancer patients.

Specifically, one patient (designated 01-002) had regression or disappearance of 20 lung metastases, but

Specifically, one patient (designated 01-002) had regression or disappearance of 20 lung metastases, and

stable disease in liver metastases (as the liver metastases were the target lesions, she did not qualify as a partial response).

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a complete response as per RECIST criteria).

Neither 03-001 or 06-001 had HLA matches with Bria-IMT™, suggesting that HLA matching

Neither 03-001 nor 06-001 had HLA matches with Bria-IMT™, suggesting that HLA matching

may not be required for clinical benefit in patients with grade I/II tumors.

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with grade I/II tumors showed evidence of clinical benefit.

the establishment of a collaboration with Incyte Corporation, this study is being altered to evaluate the combination of the Bria-IMT™

regimen with INCMGA00012 (anti-PD-1 antibody similar to KEYTRUDA®) and epacadostat (inhibitor of IDO, which suppresses the immune

The combination with KEYTRUDA® has been discontinued but may be resumed in other studies.

data confirms the “HLA Matching Hypothesis” and supports BriaCell’s strategy for the development of Bria-OTS™,

BriaCell’s first personalized off-the-shelf immunotherapy for advanced breast cancer.

the establishment of a collaboration with Incyte Corporation, this study was altered to evaluate the combination of the

Bria-IMT™ regimen with retifanlimab (anti-PD-1 antibody similar to KEYTRUDA®).

The combination with KEYTRUDA® has been discontinued.

A total of 12 patients

were treated in the phase I part of the study in combination with retifanlimab.

One of then switched from the Keytruda®

combination to the retifanlimab combination.

50% of the evaluable patients

showed disease control (stable disease or a partial response) with the safety profile again excellent.

Dosing in this study is

ongoing in the randomized phase II portion, with patients randomized either to receive Bria-IMT™ first for retifanlimab first.

Overall survival data has

been evaluated for all patients as of 2023 September 8.

The median overall survival is 13.5 months, which compares favorably with

literature reports of similar patients where overall survival has been 6.7-9.8 months (see references above).

data confirms the clinical activity of the Bria-IMT™ regimen in combination with an immune checkpoint inhibitor and justifies further

evaluation in a pivotal registration study.

and characterized by a team of dedicated scientists and clinicians, Bria-IMT™ (SV-BR-1-GM) is a targeted immunotherapy being developed

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is under development as an off-the-shelf personalized immunotherapy for advanced breast cancer.

for Bria-OTS™ comes from BriaCell’s work with Bria-IMT™, where BriaCell noted that if a patient “matches”

concept for Bria-OTS™ comes from BriaCell’s work with Bria-IMT™, where BriaCell noted that if a patient “matches”

Bria-IMT™ in their HLA type, they were more likely to respond.

HLA molecules

are the molecules that start immune responses but are polymorphic – i.e.

they are different in different people, although some

people will share the same HLA molecules (referred to as HLA alleles or HLA types).

molecules are the molecules that start immune responses but are polymorphic – i.e.

they are different in different people,

although some people will share the same HLA molecules (referred to as HLA alleles or HLA types).

is made from cell lines that are genetically engineered to expresses the immune boosters GM-CSF and interferon-α, as well as

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be selected for each patient for administration.

This approach

allows personalized treatment without the need for personalized manufacturing.

Additionally, it saves time, and skips expensive and

complicated manufacturing procedures associated with other personalized treatments.

cell lines are being engineered and transferred to good manufacturing practice (“ GMP ”) production in 2022 and

commencing clinical evaluation in 2022 (expected authorization by FDA and expected first patient to be dosed in 2022) with safety

and efficacy data expected to be released during 2022 and 2023.

is a diagnostic test that BriaCell is developing to identify the patients most likely to respond to Bria-IMT™.

Currently, BriaDx™

includes HLA typing of the patients, as patients having HLA alleles also present in Bria-IMT™ appear to have a higher likelihood

of responding to the Bria-IMT™ regimen with tumor shrinkage.

Additional markers of potential diagnostic use are being developed

based on the expression of specific biomarkers in the responder (i.e.

biomarkers which identify the patients for which Bria-IMT™

immunotherapy appears more effective) vs the non-responder patients from clinical studies of Bria-IMT™ in advanced breast cancer

and tumor samples from the patients are analyzed using cutting-edge technologies including gene expression analysis and assessment of

the levels of antibodies predicted to bind to Bria-IMTTM.

insights gained from biomarker studies conducted to date have provided us with a solid basis for the development of Bria-OTS™,

an off-the-shelf personalized immunotherapy which would match over 99% of patients with advanced breast cancer.

approach allows personalized treatment without the need for personalized manufacturing.

Additionally, it saves time, and skips expensive

and complicated manufacturing procedures associated with other personalized treatments.

cell lines are being engineered and transferred to good manufacturing practice (“ GMP ”) production and clinical evaluation

is planned to commence in 2023 (expected authorization by FDA and expected first patient to be dosed in 2023) with safety and efficacy

data expected to be released during 2023 and 2024.

Bria-OTS™ cell lines have also been engineered to express co-stimulatory molecules and additional cytokines

that can activate naïve T cells (those that have not been pre-activated).

These “Bria-OTS™ 2.0” cells are expected

to be very potent in eliciting an anticancer immune response.

Bria-OTS™ 2.0 cell lines for breast cancer and prostate cancer cells should be entering

GMP manufacturing in 2023 or early 2024.

Similar cell lines for lung cancer and melanoma will follow.

Bria-OTS™ 2.0 cell lines have the potential to transform cancer treatment as with simple intradermal injections

tailored to the individual patient, a potent and broad immune response against their cancer can be elicited, which should result in marked

destruction of the tumors by the patient’s own immune system.

Lacher M.D., Bauer G.

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Frontiers in Immunology 2018;

is being developed to help understand which patients are most likely to respond to Bria-IMT™ targeted immunotherapy.

proposed mechanism of action of Bria-IMT™, HLA molecules play a key role inducing cellular immune responses to Bria-IMT™

which boosts the patient’s immune response to their cancer.

molecules are polymorphic, in that they are different in different individuals, but shared by some individuals (similar to eye color).

Based on our clinical data to date, we hypothesize that patients with HLA alleles also present in Bria-IMT™ have a higher likelihood

of responding to the Bria-IMT™ regimen with tumor regression.

Therefore, BriaDx™, a companion diagnostic test, determines

the patients’ HLA types.

Clinical Data for Treatment with the Bria-IMT™ Regimen

conducted three Proof of Concept clinical trials, one using parental SV-BR-1 cells and the other two using Bria-IMT™ (i.e.

engineered SV-BR-1 cells – producing GM-CSF also called SV-BR-1-GM), in metastatic (i.e.

Stage IV) breast cancer patients who had

failed prior treatments.

The patients were treated with the Bria-IMT™ regimen according to the following schedule, and the results

are summarized below.

● Cyclophosphamide

300 mg/m2 intravenously 2-3 days prior to Bria-IMT™ inoculation

20 million irradiated cells given intradermally split into 4 inoculations (2 in the upper

back and 2 in the thighs)

alpha-2b 10,000 units into each inoculation site 2 and 4 days after the Bria-IMT™ inoculations

cycles every 2 weeks for four weeks (3 inoculations) then every month.

Proof of Concept Trial

Used unmodified cell line (parental

SV-BR-1 cells) + GM-CSF + cyclophosphamide.

N = 14 late stage, treatment-refractory

breast cancer patients.

No significant adverse treatment-associated

events, well tolerated.

Median Overall Survival = 12.1

Proof of Concept Trial

Used Bria-IMT™

genetically engineered SV-BR-1 cells – producing GM-CSF) with pre-dose, low dose cyclophosphamide and post-dose local

interferon-α to boost the response (the Bria-IMT™ regimen) with cycles every two weeks for four weeks (three inoculations)

then monthly up to a total of six cycles.

late stage, treatment-refractory (3 breast cancer (2 grade II and 1 grade III), and 1 ovarian cancer) patients.

No significant

adverse treatment-associated events, well tolerated.

Overall Survival = 35 months.

responder with greater than 90% regression during treatment and a subsequent relapse (upon halting treatment) responded to re-treatment.

matched Bria-IMT™ at a key HLA type (HLA-DR) and had a grade II tumor.

Proof of Concept Trial

patients were screened, 24 enrolled and 23 dosed in the Phase I/IIa study (2017-2018).

The Bria-IMT™

regimen included pre-dose low-dose cyclophosphamide (to reduce immune suppression), intradermal inoculation with 20-50 million irradiated

Bria-IMT™ cells between two and three days later, with subsequent intradermal inoculation with interferon-α2b approximately

two and four days later.

The majority of adverse events (“ AEs ”) were limited to expected minor local irritation

at the injection sites.

patients treated with this regimen received cycles every two weeks for the first month and then monthly.

They were heavily pre-treated

with a median of four prior systemic therapy regimens.

were treated with a median of three cycles of therapy (range 1-8).

The Bria-IMT™

regimen was able to elicit both cellular immune responses (as evidenced by DTH responses in 85% of patients evaluated) and antibody

responses (present in 58% of patients evaluated).

were no serious, unexpected, drug-related AEs.

patients who withdrew from the trial did so due to the worsening of their underlying disease.

Specifically, 14 patients terminated participation

due to progressive disease, four withdrew, three terminated participation due to mortality (unrelated to study drug), and two terminated

participation due to adverse events (both judged unrelated to study drug).

the combined experience of the second and third studies (which both use the same Bria-IMT™ regimen), disease control (i.e.

disease or partial response) was evaluated.

Disease control was seen in

four of twenty patients who match with Bria-IMT™ at one or more HLA locus, including in three of six patients who match Bria-IMT™

at two or more HLA loci, further supporting our “HLA Matching Hypothesis”, and the development of Bria-OTS ™ to

single match over 99% and double match approximately 90% of the patient population.

Effectiveness also depends

on the ability of the patient to develop an immune response to Bria-IMT™, as measured by DTH to the Bria-IMT™ or to the

parental cell line (SV-BR-1).

Across both “monotherapy” studies (SVMC #01-026 and WRI-GEV-007), a positive DTH response

was noted in 22 patients while five were not responsive.

Results are shown in the tables

below, combining the second and third proof of concept studies, both of which used Bria-IMT™ in an identical regimen.

Control* in Studies SVMC #01-026 and WRI-GEV-007 Based on HLA Matching to Bria-IMT™ and Immune Response to Treatment

Disease Control

Disease Control in Immune Responders

All Patients N=27

Control in Studies SVMC #01-026 and WRI-GEV-007 Based on Tumor Grade

Patients N=27

Responders (as measured by DTH)

Responders N=22

was dosed in 27 patients (four in 2004-2006, 23 in 2017-2018) as the Bria-IMT™ regimen alone.

has been very well tolerated (over 100 doses given to date).

regression was seen in patients who were able to mount an immune response and matched Bria-IMT™ at HLA types, confirming our

main hypothesis and supporting using HLA typing as a marker to predict who is most likely to respond.

continues to monitor their clinical trials, proposing that BriaDx™ would include HLA typing as well as other potential biomarkers

(such as tumour grade or the ability to mount a DTH response) to identify the patients most likely to respond to the Bria-IMT™

of Additional Immunotherapy Cell Lines

on these observations, BriaCell is extending this technology to other types of cancer by developing additional immunotherapy cell

currently being genetically engineered include a breast cancer cell line, a prostate cancer cell line, a non-small cell lung cancer

cell line and a melanoma cell line.

steps in the genetic engineering have been completed with subsequent steps planned for 2022 and 2023.

for these immunotherapy cell lines are anticipated starting in 2022.

Kinase C Delta (PKCδ) Inhibitors

delta isoform of the Protein Kinase C family (PKCδ) is implicated in a multitude of cellular responses to external and internal

stimuli, playing both pro- and anti-tumorigenic roles.

In contrast to PKCα, PKCδ does not seem to be required for survival

of normal cells.

In PKCδ knockout mice, mild lymphoproliferation was observed, but overall, PKCδ inhibition is well tolerated

at the organismal level.

BriaCell scientists develop small-molecule PKCδ inhibitors for use in those situations where PKCδ

carries out pro-tumorigenic functions.

Preliminary data suggest that PKCδ inhibition may be particularly beneficial in a subset

of cancers with oncogenic Ras or with otherwise activated Ras signaling, for instance in endometrial cancers with estrogen-induced K-Ras

stabilization.

In particular, PKCδ inhibition may be of therapeutic use in cancers dependent on Ras signaling for proliferation,

as shown in vitro for lung cancer.

BriaCell, through our subsidiary Sapientia, uses structural information of Rottlerin, a PKCδ

inhibitor with modest activity, and Staurosporine, a potent but nonspecific PKC inhibitor, to develop a series of “hybrid”

This rational design approach is envisioned to yield molecules with, compared to Rottlerin, enhanced activity yet retained

PKC δ-selectivity.

inhibition was achieved with small molecules using a pharmacophore model based on Staurosporine and Rottlerin.

One of the most promising

molecules based on this approach, BC106 (BJE6-106), presents an IC 50 for PKCδ inhibition of approximately 50 nM and

is approximately 1000-fold more selective for PKCδ than for PKCα.

In cellular and animal model studies, BC106 shows effective

anti-proliferative and anti-tumor activity, but this molecule is not water soluble, hence not appropriate as a drug candidate.

to improve water solubility have been initiated, with a series of compounds undergoing testing in in vitro kinase and cell-based

develop PKCδ inhibitors, BriaCell affiliates started with two molecules known to have PKC-inhibitory properties:

Staurosporine

and Rottlerin.

Multiple chemical manipulations and testing resulted in BC106, one of the Company’s most effective compounds to-date.

Staurosporine is a well-known PKC inhibitor with anti-cancer activity, while Rottlerin, also known as Mallotoxin, opens potassium channels

that have been used to induce apoptosis.

Rottlerin has also been shown to be an immunosuppressive agent, affecting multiple oncogenic

Although some reports claim that Rottlerin does not act primarily via PKCδ inhibition, BriaCell’s data supports

Rottlerin-derived molecules as viable tumor suppressors.

Company’s strategy for compound synthesis is based on a hitherto unexplored design concept, wherein functional moieties of two

natural products known to strongly inhibit PKCδ – Rottlerin and Staurosporine – have been “intellectually cut”

from each natural product and then covalently joined to make a novel, chimeric scaffold.

The Company’s synthetic analogs, in essence,

combine the bottom benzopyran moiety of Rottlerin and chemically join that to the indolyl carbazole moiety of Staurosporine.

new chimeric scaffolds are synthesized in a novel, convergent modular fashion, allowing for the rapid assembly and testing of many derivatives.

was initially used because this molecule inhibits purified PKCδ at an IC 50 of 3-5 μM in vitro , and in cultured

cells with an IC 50 of 5 μM.

Rottlerin is relatively more selective for PKCδ than for PKCα (PKCδ IC 50 :PKCα

IC 50 ≈ 1:30).

BriaCell further advanced our pharmacophore model using the Rottlerin-based prototype chimeric structure

in combination with Staurosporine by incorporating protein structural data for the novel class PKCs.

This strategy produced a second

generation of PKCδ inhibitors with the “head” group resembling that of Staurosporine and the other domains conserved

from the Rottlerin scaffold to preserve isozyme specificity.

A second generation successful product is represented by BC128, which has

an IC 50 of 4 μM for PKCδ (similar to Rottlerin), and better isozyme selectivity (IC 50 of >120 μM

BC128 showed anti-tumor cell activity in vitro and in vivo .

BriaCell’s most-recent “lead” compound, produces substantial cytotoxicity against multiple human tumor lines at nM

concentrations (10-40 times lower than Rottlerin or BC128).

BC106 dramatically inhibited the clonogenic capacity of RAS-mut tumor cell

lines after as little as 12 hours of exposure.

BC106 is 1000-fold more selective for PKCδ than for PKCα.

The latter is an

important finding because inhibition of PKCα is generally toxic to all cells (normal and malignant) and would make BC106 non-tumor-targeted.

Approximately

40% of melanomas harbor NRAS mutations and there is no effective RAS-targeted treatment available for this subgroup.

BriaCell affiliates

have demonstrated that NRAS-mutant melanoma cells were highly sensitive to PKCδ siRNA knock-down and to BC106 at nM concentrations.

Clonogenic assays demonstrated that irreversible inhibition of proliferation required as little as 12 hours of exposure to Rottlerin

affiliates also assessed the effects of PKCδ inhibition on breast tumor growth and survival in a xenograft human breast cancer

stem cell model.

PKCδ inhibition prevented tumor grown and promoted the survival of the animals evaluated over the course of 300

days (note that the vehicle treated animals all died within the first 20 days of the study).

PKCδ inhibition also inhibited the growth of neuroendocrine cells.

and Outlook – Early Stage Preclinical Program

percent of all human malignancies display activating RAS mutations, with another 60% showing over-activity of Ras-signaling pathways.

novel, proprietary PKCδ inhibitors have shown activity against multiple RAS transformed tumors.

has an attractive safety profile based on in vivo studies and knock out mouse studies.

also has potential activity as an immunotherapeutic by blocking TGFβ signaling.

inhibitors are applicable to specific niche tumor types which provide an accelerated clinical development plan.

aspects of first-generation inhibitor rottlerin and staurosporine ([a] pan-PKC inhibitor) were combined to create second generation

inhibitor KAM1.

generation inhibitors such as BC-106 have improved potency and selectivity.

generation inhibitors are under development to optimize their drug-like characteristics.

PKCδ inhibitors lack endothelial cell cytotoxicity, while PKCδ deficient mice develop normally and are fertile.

that there is no marked intrinsic toxicity as a result of inhibiting PKCδ.

selection is anticipated in 2022.

Prior IA, Lewis PD, Mattos C.

A comprehensive survey of Ras mutations in cancer.

Xia, S., Forman, L.

Protein Kinase Cδ Is Required for Survival of Cells Expressing Activated p21 RAS .

282, 13199–13210 (2007);

Protein kinase Cδ inactivation inhibits cellular proliferation and

decreases survival in human neuroendocrine tumors.

Cancer 18, 759–71 (2011);

Xia, S., Chen, Z., Forman, L.

PKCδ survival signaling in cells containing an activated p21Ras protein requires PDK1.

S., Chen, C.-Y., Chen, J.

Oncogenic Ras Mediates Apoptosis in Response to Protein Kinase C Inhibition

through the Generation of Reactive Oxygen Species.

275, 39001–39011 (2000);

Characterization of p21Ras-mediated apoptosis induced by protein kinase C inhibition and application to human tumor cell lines.

198, 277–294 (2004);

Y., Liou, J., Forman, L.

Differential regulation of discrete

apoptotic pathways by Ras.

273, 16700–9 (1998);

Direction of p21ras-generated signals

towards cell growth or apoptosis is determined by protein kinase C and Bcl-2.

Oncogene 11, 1487–98 (1995);

Phosphorylation of Bcl-2 protein and association with p21Ras in Ras-induced apoptosis.

271, 2376–9 (1996);

Chen, C.-Y., Liou, J., Forman, L.

Correlation of genetic instability and apoptosis in the presence of oncogenic

Cell Death Differ.

5, 984–995 (1998);

The recruitment of Fas-associated death domain/caspase-8 in Ras-induced

Cell Growth Differ.

12, 297–306 (2001).

Miyamoto A, Nakayama K, Imaki H, Hirose S, Jiang Y, Abe M, Tsukiyama T, Nagahama H, Ohno S, Hatakeyama S, Nakayama KI.

proliferation of B cells and auto-immunity in mice lacking protein kinase Cdelta.

2002 Apr 25;416(6883):865-9.

Wermuth PJ, Addya S, Jimenez SA.

Effect of Protein Kinase C delta (PKC-δ) Inhibition on the Transcriptome of Normal and Systemic

Sclerosis Human Dermal Fibroblasts In Vitro.

PLoS ONE, November 2011, Volume 6, Issue 11, e27110;

Li Z, Jimenez SA.

Protein Kinase C δ and c-Abl Kinase Are Required for Transforming Growth Factor β Induction of Endothelial–Mesenchymal

Transition In Vitro.

Arthritis and Rheumatism, Vol.

8, August 2011, pp 2473–2483 PMCID:

Bujor AM, Asano Y,

Haines P, Lafyatis R, Trojanowska M.

The c-Abl Tyrosine Kinase Controls Protein Kinase C δ –Induced Fli-1 Phosphorylation

in Human Dermal Fibroblasts.

Arthritis & Rheumatism, Vol.

6, June 2011, pp 1729–1737.

lines currently being genetically engineered include a breast cancer cell line, a prostate cancer cell line, a non-small cell lung

cancer cell line and a melanoma cell line.

The genetic engineering has been completed for the breast cancer cell line and GMP manufacturing completed.

Release testing

is underway with the goal to initiate clinical studies in 2H2023.

The prostate cancer cell line is expected to initiate GMP manufacturing

in late 2023 or early 2024 with the lung cancer and melanoma cell lines to follow.

filings for these immunotherapy cell lines are anticipated starting in 2023.

Phase Programs

is developing multi-specific binding reagents that simultaneously bind to an immune cell and a cancer cell, or just to a cancer cell,

and activate the immune system against the cancer cells.

The novel binding reagents are designed to act, among others, as potent immune

cell activators/immune checkpoint inhibitors without the toxicity of current checkpoint inhibitors.

The expected effect is a highly targeted

therapy envisioned to selectively destroy cancer cells without affecting normal (i.e.

non-cancerous) cells.

This may mean less severe

side effects for the treated cancer patients compared to alternative therapies.

The Company cautions that these novel therapeutics are

still in early-stage research and development and is not making any express or implied claims as to their success in cancer treatment

or commercial viability.

The patent application seeks protection for, among others, the design of new therapeutics and methods for their

These are designated “Bria-TILs-Rx”.

IND filings for Bria-TILs-Rx for the treatment of prostate cancer and epithelial

and glandular cancer, respectively, are anticipated to be made in 2022 and require an additional cost of approximately US$1,000,000 each.

October 28, 2020, BriaCell entered into a Cooperative Research and Development Agreement (“ CRADA ”) with the U.S.

of Health and Human Services, as represented by the NCI.

Under the CRADA, NCI and BriaCell will work together to conduct preclinical

studies to develop and test BriaCell’s proprietary Bria-OTS cellular immunotherapy as a treatment for cancer, to improve and broaden

applicability of this therapeutic strategy.

Under the terms of the CRADA, BriaCell will provide funding (totaling $433,400 over three

years) to support the project.

The NCI estimates that 1.3 person-years of effort per year will be required to complete the CRADA research,

which includes the development of a mouse model of this therapeutic strategy.

BriaCell and NCI will be using their combined expertise

in tumor immunology, molecular biology and development of cellular therapies to design studies which are intended to trigger the immunologic

pathways necessary to create potent immune responses against cancer.

The goal of the collaboration is to develop novel therapeutics for

future clinical collaborations, allowing cancer patients to potentially benefit from potent and personalized cancer immunotherapy.

of Action of Bria-IMT™ and Bria-OTS™ 4

mechanism of action of Bria-IMT™/Bria-OTS™ is currently under investigation.

believe that Bria-IMT™/Bria-OTS™ activates the patient’s immune system to recognize tumor cells and destroy them.

hypothesize that Bria-IMT™/Bria-OTS™ exerts its action via the patient’s antigen-presentation system (i.e.

that presents antigen material on the surface of cells for recognition by the T cells of the immune system as either self (i.e.

or foreign (i.e.

to be destroyed)).

Specifically, Bria-IMT™/Bria-OTS is thought to stimulate dendritic cells, a key component of

the antigen-presenting system, to display certain immunogenic (i.e.

immune response-generating) protein fragments to T cells, which activates

the T cells to destroy the tumor cells either directly, or indirectly by inducing a humoral (i.e.

antibody-generating) immune response.

In addition, we also have shown that Bria-IMT™ is capable of directly stimulating T cells, thereby potentially adding additional

therapeutic benefits.

The latter property of Bria-IMT™ is the basis of the Bria-OTS™ project as it requires HLA matching

between the therapeutic cells and the patient.

preliminary analyses have shown several up-regulated genes in Bria-IMT™ that encode proteins known to be immunogenic (i.e.

response-generating), suggesting that Bria-IMT™ can stimulate the immune system against the cancer cells.

is a human breast cancer cell line which expresses Her2/neu (a protein well known for its overexpression in breast cancer but also associated

other epithelial malignancies, including ovarian, pancreatic, colon, bladder and prostate cancers).

Bria-IMT™ has been engineered

to produce and secrete GM-CSF, a protein that promotes dendritic cell function, a key component of the immune system, and hence activates

the immune system.

Mechanisms of Specific Immune Activation in Advanced Breast Cancer

Bria-IMT/OTS™ produces

breast cancer antigens (i.e.

proteins made by breast cancer cells).

Bria-IMT/OTS™ secretes

GM-CSF, which further promotes dendritic cell-based antigen presentation (i.e.

boosts the response).

Breast cancer antigens

are taken up by dendritic cells and “presented” to CD4+ and CD8+ T cells implicated in tumor destruction.

Bria-IMT/OTS™ directly

stimulates cancer fighting CD4+ and CD8+ T cells (i.e.

further boosts the response).

Bria-IMT/OTS™ biological

activity depends on HLA matching of Bria-IMT/OTS™ and the patient.

I/IIA Combination Study of Bria-IMT™ with Immune Checkpoint Inhibitors in Advanced Breast Cancer

FDA approved the combination study of Bria-IMT™ with immune checkpoint inhibitors in advanced breast cancer (third line or later).

The initial study used pembrolizumab (KEYTRUDA®, purchased by the Company as the Company does not have an agreement with Merck for

the supply of KEYTRUDA®).

The Company dosed 11 patients with this combination and no dose limiting toxicities were observed.

Additionally,

evidence of additive or synergistic activity was observed.

combination with KEYTRUDA® was discontinued and the study was subsequently modified to use a combination of Bria-IMT with the Incyte

PD-1 inhibitor retifanlimab (INCMGA00012).

The Company anticipates additional safety and efficacy data for the combination of Bria-IMT™

with INCMGA00012 to be released throughout 2022 and 2023.

Lacher M.D., Bauer G.

Fury B., Graeve S., Fledderman E.L., Petrie T.D., Coleal-Bergum D.P., Hackett T., Perotti N.H., Kong Y.Y.,

Kwok W.W., Wagner J.P., Wiseman C.L., and Williams W.V.

SV-BR-1-GM, a Clinically Effective GM-CSF- Secreting Breast Cancer Cell Line,

Expresses an Immune Signature and Directly Activates CD4+ T Lymphocytes.

Frontiers in Immunology 2018;

the year ended July 31, 2022, research costs amounted to $8,021,489 as compared to $2,020,899 for the year ended July 31, 2021.

is attributed to the recommencing of the Company’s clinical trials and the increased activity in the lab, including the hiring

of additional lab employees.

may face difficulties recruiting or retaining patients in our ongoing and planned clinical trials if patients are affected by the virus

or are fearful of visiting or traveling to our clinical trial sites because of the outbreak of COVID-19.

In the event that clinical trial

sites are slowed down or closed to enrollment in our trials, this could have a material adverse impact on our clinical trial plans and

We are continuing to assess our business plans and the impact COVID-19 is having on our clinical trial timelines and our ability

to recruit candidates for clinical trials, but there can be no assurance that this analysis will enable us to avoid part or all of any

impact from the spread of COVID-19 or its consequences, including downturns in business sentiment generally or in our sector in particular.

The extent to which COVID-19 and global efforts to contain its spread will impact our operations will depend on future developments,

which are highly uncertain and cannot be predicted at this time, and include the duration, severity and scope of the outbreak and the

actions taken to contain or treat the coronavirus outbreak.

We currently believe that the execution of our clinical trials and research

programs will be delayed by at least one quarter due to COVID-19.

patient transitioned from combined treatment of the Bria-IMT™ regimen with KEYTRUDA® to combination treatment with retifanlimab.

She has continued to have stable disease, with further reduction in the size of some of her breast cancer nodules around the brain, including

disappearance of one nodule behind the left eye which was causing proptosis (i.e.

pushing the eye forward).

This nodule has completely

disappeared and her eye has gone back into place.

for the Combination Study of Bria-IMT™ with Immune Checkpoint Inhibitors

checkpoint inhibitors, such as anti-PD-1 antibodies, have come to the forefront in the fight against cancer, with substantial benefits

for some patients.

Recently, the significance of immune checkpoint inhibitors was recognized by the Nobel committee by awarding Dr.

Honjo and Dr.

Allison with the 2018 Nobel Prize in Physiology or Medicine (scientists behind game-changing cancer immunotherapies

win Nobel medicine prize) , validating the Company’s decision to initiate a combination therapy with immune checkpoint

Allison and Honjo independently, using different strategies, showed a new approach of treating patients by awakening certain cells of

the immune system, T cells, to attack tumors.

This new approach of treating patients with immune checkpoint inhibitors (such as anti-PD-1

antibodies), designed to overcome immune suppression in cancer patients, is revolutionizing the fight against cancer.

2010, a pre-clinical study by Dr.

Allison’s research group showed that combination with anti-PD-1 antibodies potentiated the tumor-destroying

effect of melanoma cells engineered to produce GM-CSF, a substance that activates the immune system, compared to the treatment with the

GM-CSF producing cells alone.

Bria-IMT™, a breast cancer cell line, also produces GM-CSF.

Bria-IMT™ has been shown to indirectly

and directly stimulate T cells, and hence has displayed immune-activating properties.

BriaCell has published these findings in a leading

immunology journal.

It is important to note that anti-PD-1 antibodies have not been shown to work on their own in breast cancer.

(pembrolizumab)

by Merck & Co., Inc., KEYTRUDA® (pembrolizumab) is a prescription medicine that may treat certain cancers by working with the

immune system.

It has been approved for the treatment of a number of cancer indications, excluding breast cancer.

The company is not

a party to any agreements with Merck for the supply of KEYTRUDA®.

A phase I/IIa study was

performed evaluating the combination of the Bria-IMT™ regimen with KEYTRUDA® (pembrolizumab).

This combination combines

the induction of an immune response by Bria-IMT™ (putting the foot on the gas of the immune response) with the ability of KEYTRUDA®

to block the PD-1 – PD-L1 immune checkpoint (i.e.

taking the foot off the brakes of the immune response).

Eleven patients with advanced

breast cancer (with a median of four prior systemic therapy regimens) were treated with this regimen, with cycles every three weeks

for a median of three cycles each (range:

1 – 9 cycles).

Two patients had evidence

of tumor regression, both of whom had grade II tumors and also had robust immune responses (as measured by DTH) to Bria-IMT™.

One matched Bria-IMT™ at two HLA types while the other did not match Bria-IMT™ at any HLA types, suggesting that the

Bria-IMT™ regimen, when given in combination with a PD-1 inhibitor, may be able to induce tumor regression without an HLA match,

especially in patients with grade I/II tumors.

One other patient in this cohort had a grade II tumor and that patient had stable

Thus, of the three patients with grade I/II tumors treated with the combination of the Bria-IMT™ regimen with pembrolizumab,

all three showed evidence of a clinical benefit, as typically defined in clinical research.

BriaCell purchased the KEYTRUDA®

for this study without a collaboration with Merck while pursuing other avenues to collaborate with a company that has an anti-PD-1

antibody and/or other immune checkpoint inhibitors to use in combination with the Bria-IMT™ regimen.

BriaCell has obtained

such an agreement with Incyte Corporation as noted below.

Based on this, the combination therapy study (BRI-ROL-001) had been amended

to evaluate combination of the Bria-IMT™ regimen with Incyte’s PD-1 inhibitor as noted below.

The combination

with KEYTRUDA® has been discontinued.

& Incyte Collaboration and Supply Agreement

following summarizes the non-exclusive clinical trial collaboration to evaluate the effects of combinations of novel clinical candidates:

The clinical study focuses

on BriaCell’s lead candidate, Bria-IMT™, in combination with Incyte’s retifanlimab, for treatment of advanced

breast cancer.

Incyte is providing retifanlimab,

an anti-PD-1 monoclonal antibody, for use in combination studies with BriaCell’s lead candidate, Bria-IMT ™.

Incyte is a global biopharmaceutical

company focused on discovering and developing novel therapeutics in oncology and other serious diseases.

The first twelve patients

will receive the Bria-IMT™ regimen in combination with retifanlimab.

Once safety of the combination has been established, an

expansion cohort of 24 subjects will be evaluated.

This expansion cohort will be limited to patients who match Bria-IMT™

at one or more HLA alleles and/or have Grade I/II disease.

Dosing of the novel combinations

commenced in the fourth quarter of 2019 and is ongoing.

The Company anticipates

safety and efficacy data to be released during 2022 and 2023.

Pending discussions with

Food and Drug Administration (“ FDA ”), a registration study focused on, but not limited to, Bria-IMT™,

in combination with Incyte’s selected compounds for advanced breast cancer, is planned to commence in late 2022 or early 2023

with the Bria-OTS™ program following by approximately 8-10 quarters.

data was presented at the American Association for Cancer Research San Antonio Breast Cancer Meeting on December 10-11, 2020.

presented summarized the clinical and pathological data of the Bria-IMT™ monotherapy (i.e.

the Bria-IMT™ regimen alone) study

and the Phase I/IIa clinical study of Bria-IMT™ in combination with immune checkpoint inhibitors, including pembrolizumab (KEYTRUDA®;

manufactured by Merck & Co., Inc.), and more recently, Incyte’s retifanlimab (developed by Incyte Corporation), in advanced

breast cancer.

Thirty patients were treated with the Bria-IMT™ regimen (19 with the Bria-IMT™ regimen alone, four who began

on the Bria-IMT™ regimen and transitioned to a combination of Bria-IMT™ with Incyte’s retifanlimab, and seven with

a combination of Bria-IMT™ with KEYTRUDA®).

Eleven of those patients had moderately-well differentiated tumors.

Seventy percent

of these patients who were able to develop an immune response showed disease control, suggesting that Bria-IMT™, with a molecular

signature most closely related to moderately-well differentiated tumors, may result in disease control, especially in patients with moderately-well

differentiated tumors.

These patients were very heavily pre-treated with a median of seven prior systemic therapy regimens (including

chemotherapy, biological and “targeted” therapy).

The median PFS of this cohort was 5.7 months in the monotherapy study,

and 6.9 months in combination therapy.

Of the group, there were nine patients with evaluable lesions including six with stable disease

and two with partial responses according to RECIST criteria.

One patient with stable disease had a marked reduction in numerous non-target

The data suggests clinical and survival benefits for patients with moderately-well differentiated tumors who were treated with

the Bria-IMT™ regimen with or without check point inhibitors.

Notably, the survival benefit was higher in the group that received

the Bria-IMT™ regimen with check point inhibitors, suggesting an additive or synergistic effect.

median OS for the combined monotherapy and combination therapy was 12.5 months (data on six patients with moderately-well differentiated

An OS of 7.2-9.8 months in similar patients with metastatic breast cancer in the third line setting has recently been published

(Kazmi S, et al.

“Overall survival analysis in patients with metastatic breast cancer and liver or lung metastases treated with

eribulin, gemcitabine, or capecitabine.” Breast Cancer Res Treat.

This suggests a potentially significant survival benefit

for the patients treated with the Bria-IMT™ regimen alone or in combination with check point inhibitors.

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.

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.

are listed as the following:

USPN 8,956,619 B2;

USPN 9,650,429 B2;

USPN 10,377,810 B2

an important co-stimulatory molecule present on antigen-presenting cells and key for activating T cells.

CD80 also acts as an immune checkpoint

As noted in the patents, significant data has been generated showing that in animal models sCD80 is capable of enhancing anti-cancer

immune responses and shrinking tumors in model systems.

The sCD80 appears to act both as an immune stimulator and checkpoint inhibitor.

This makes it an ideal candidate to combine with BriaCells’s cellular immunotherapy platform.

Current timelines project that the sCD80 may be ready to enter the clinic in early 2025.

and Sales Strategy

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This formulation will permit stockpiling

of the immunotherapy so that it can be sent on demand to clinical sites.

The 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

of immunotherapy so that it can be sent on demand to clinical sites.

The 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

Commercial Considerations

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We have been working with KBI Biopharma, Inc.

(“ KBI ”) 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.

(“KBI”) 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.

ER/PR-) and adventitious agents to rule out contamination with infectious agents.

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.

Additional manufacturing facilities

have been evaluated and may be enlisted as demand grows.

will target oncologists who are well-versed in the use of immunotherapy and especially breast cancer treatment centers.

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late stage breast cancer, either by direct outreach or by partnering with another company that has an established presence in the oncology

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.

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.

July 24, 2017, the Company entered into a Share Exchange Agreement with its wholly-owned subsidiary, BriaCell Therapeutics Corp., Sapientia,

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part of the Transaction, BriaCell acquired the license agreement Sapientia entered into with Faller-Williams Technology (“FWT”),

dated March 16, 2017, (the “ License Agreement ”), pursuant to which BriaCell acquired all rights, including composition

of matter patents (the “ PKCδ Patents ”), and preclinical study data to a novel therapeutic technology platform,

PKCδ inhibitors, which represents a unique, highly-targeted approach to treat cancer and to boost the immune system.

dated March 16, 2017, (the “License Agreement”), pursuant to which BriaCell acquired all rights, including composition of

matter patents (the “PKCδ Patents”), and preclinical study data to a novel therapeutic technology platform, PKCδ

inhibitors, which represents a unique, highly-targeted approach to treat cancer and to boost the immune system.

to the License Agreement, FWT is eligible to receive certain milestone payments, including i) $5,000,000 upon the filing of each New

Drug Application with the FDA with respect to products disclosed and/or described in the PKCδ Patents (the “ PKCδ

Drug Application with the FDA with respect to products disclosed and/or described in the PKCδ Patents (the “PKCδ Products”);

ii) $25,000,000 upon final approval of each New Drug Application by the FDA for the marketing of a PKCδ Product;

iii) $1,000,000 upon the filing of each Marketing Authorization Application (“ MAA ”) with the Medicines and Healthcare

Products Regulatory Agency of United Kingdom or the Committee for Medicinal Products for Human Use of the European Commission with respect

to a PKCδ Product;

and iv) $5,000,000 upon the final approval of each MAA with the Medicines and Healthcare Products Regulatory

Agency of United Kingdom or the Committee for Medicinal Products for Human Use of the European Commission for the marketing of a PKCδ

iii) $1,000,000

upon the filing of each Marketing Authorization Application (“MAA”) with the Medicines and Healthcare Products Regulatory

Agency of United Kingdom or the Committee for Medicinal Products for Human Use of the European Commission with respect to a PKCδ

and iv) $5,000,000 upon the final approval of each MAA with the Medicines and Healthcare Products Regulatory Agency of United

Kingdom or the Committee for Medicinal Products for Human Use of the European Commission for the marketing of a PKCδ Product.

is eligible to receive certain royalty payments under the License Agreement.

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with the United States Patent and Trademark Office (“USPTO”) on June 14, 2004, U.S.

7,674,456 B2, includes

claims to the following:

Compositions comprising

Therapeutic methods of

using said compositions

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.

In essence, it 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.

7,674,456 B2, includes claims

to the following:

comprising SV-BR-1 cells

methods of using said compositions

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 (BriaDx™).

The PCT application entered the National Phase in the second half of 2018 and

was granted in Japan on June 21, 2021.

was recently awarded an Australian patent (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.).

BriaCell has also received an Issue Notification from the USPTO for the composition of matter and method of use of

its personalized off-the-shelf cell-based immunotherapy for cancer.

The patent was issued on January 24, 2023 as US Patent No.

B2 with the term extending to May 25, 2040.

July 24, 2017, BriaCell obtained the exclusive license to certain patents related to PKCδ inhibitor technology, including patents

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of the date of this filing, we had eleven full-time employees and one part-time employee, located in various US states including:

NY, CA, PA, SC, HI, and NJ.

CA, PA, SC, HI, and NJ.

We also have international employees located in Canada and Israel.

the year ended July 31, 2022, the average number of employees has been eight, of whom four were executive management.

the year ended July 31, 2023, the average number of employees has been sixteen, of whom four were executive management (July 31, 2022 – eight).

and Development Activities and Costs

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resources and third-party consultants to manage our manufacturing contractors.

is currently manufactured under current Good Manufacturing Practices (“ cGMP ”) pursuant to agreements with UC Davis

and with KBI, which is located in The Woodlands, Texas.

is currently manufactured under current Good Manufacturing Practices (“cGMP”) pursuant to agreements with UC Davis and with

KBI, which is located in The Woodlands, Texas.

June 11, 2015, the Company entered into an Agreement for Services with The Regents of the University of California, acting for and on

4 unchanged sentences

doses suitable for cold chain shipment (the “KBI Services”).

The Company pays for the cost of materials, consumables,

and third party services, plus an additional 5% fee to compensate KBI for the cost of purchasing, material handling, inventory and administration

The Company pays for the cost of materials, consumables, and

third party services, plus an additional 5% fee to compensate KBI for the cost of purchasing, material handling, inventory and administration

and management of third party services necessary for KBI to perform the KBI Services.

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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.

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

and Marketing

5 unchanged sentences

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 .

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.

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

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(“GLP”) regulations;

to the FDA of an Investigational New Drug Application (“ IND ”), which must become effective before clinical trials

may begin and must be updated annually or when significant changes are made;

by an independent Institutional Review Board (“ IRB ”) or ethics committee at each clinical site before the trial

to the FDA of an Investigational New Drug Application (“IND”), which must become effective before clinical trials may

begin and must be updated annually or when significant changes are made;

by an independent Institutional Review Board (“IRB”) or ethics committee at each clinical site before the trial is begun;

of adequate and well-controlled human clinical trials to establish the safety, purity and potency of the proposed biologic product

candidate for its intended purpose;

of and submission to the FDA of a Biologics License Application (“ BLA ”), after completion of all pivotal clinical

of and submission to the FDA of a Biologics License Application (“BLA”), after completion of all pivotal clinical trials;

completion of an FDA Advisory Committee review, if applicable;

a determination

by the FDA within 60 days of its receipt of a BLA to file the application for review;

determination by the FDA within 60 days of its receipt of a BLA to file the application for review;

completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the proposed product is produced

1 unchanged sentence

continued safety, purity and potency, and of selected clinical investigations to assess compliance with current Good Clinical Practices

and approval of the BLA to permit commercial marketing of the product for particular indications for use in the United States, which

must be updated annually when significant changes are made.

review and approval of the BLA to permit commercial marketing of the product for particular indications for use in the United States,

which must be updated annually when significant changes are made.

testing and approval process requires substantial time, effort and financial resources, and we cannot be certain that any approvals for

30 unchanged sentences

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.

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.

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

164 unchanged sentences

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.

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.

addition, there has been a recent trend of increased federal and state regulation of payments made to physicians and other healthcare

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.

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 .

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.

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.

may also be subject to data privacy and security regulation by both the federal government and the states in which we conduct our business.

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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.

states resulting from the national implementation of underlying E.U.

In all cases, the clinical trials are conducted in

accordance with GCP and other applicable regulatory requirements.

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.

In all cases, the clinical trials are conducted in accordance

with GCP and other applicable regulatory requirements.

obtain regulatory approval of a new drug or medicinal product in the E.U., a sponsor must obtain approval of a marketing authorization

64 unchanged sentences

trials, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.

Appoints Renowned Oncologist, Giuseppe Del Priore, MD, MPH, as Chief Medical Officer

February 16, 2022, the Company announced its appointment of Giuseppe Del Priore, MD, MPH, as the Company’s Chief Medical Officer

Del Priore will oversee the clinical and regulatory aspects of BriaCell’s current and upcoming

clinical trials, including the ongoing Phase I/IIa combination study of BriaCell’s lead candidate, Bria-IMT™, with Incyte’s

checkpoint inhibitor, retifanlimab, in advanced breast cancer.

Del Priore is a seasoned healthcare executive with over 25 years of experience in research, drug development, and clinical trials management.

Del Priore’s prior work experience includes serving as a C-Suite biotechnology executive, a National Director at the Cancer

Treatment Centers of America, and faculty at Indiana University School of Medicine, Weill Cornell Medicine, and New York University School

Del Priore completed his MPH degree in Biostatistics and Epidemiology at the University of Illinois Chicago School of

Public Health, his medical degree with Distinction at The State University of New York, and his BA, magna cum laude, in Philosophy, at

The City University of New York, with additional training at Memorial Sloan Kettering Cancer Center, The University of Chicago, Northwestern

University, and the University of Rochester.

He has authored numerous publications, was named on several patents, and was listed as the

“Best Doctors” by the U.S.

News & World Report.

He regularly appears in various media outlets as a Key Opinion Leader

His work has been reported on by CNN, NY Times, Bloomberg, NPR, and countless worldwide outlets and has earned editorial

comments from leaders at MSKCC just in the past year.

Appoints Leading Immunologist Dr.

Alexander Kharazi to its Scientific Advisory Board

February 23, 2022, the Company announced its appointment of leading immunologist, Alexander Kharazi, M.D., Ph.D., to its Scientific Advisory

Kharazi co-invented Bria-IMT™, BriaCell’s lead clinical candidate, in collaboration with Dr.

BriaCell’s Founder and Principal Research Advisor.

Kharazi currently serves as Chief Technology Officer at Stemedica Cell Technologies,

His experience includes roles as Chief Scientist of the Immunotherapy laboratory at St.

Vincent Medical Center in Los Angeles (1998-2006)

and Chief Pathologist of a large good laboratory practice animal study at the University of California, Los Angeles (UCLA) (1991-1998)

reporting results to the U.S.

Additionally, he has worked as a Research Fellow in the department of Pathology at the Tokyo

Metropolitan Institute of Gerontology in Japan from 1989 to 1991.

Kharazi earned his Ph.D.

in immunology and his medical degree in

internal medicine and pathology in Kiev, Ukraine.

He is a named inventor on eight U.S.

patents and several foreign patents.

author of numerous U.S.

and international publications and has been an invited speaker/chairman/panelist on several scientific meetings.

Adds Two Clinical Trial Sites to Accelerate Patient Enrollment

February 28, 2022, the Company announced it has recruited two additional clinical sites for screening and enrolling advanced breast cancer

patients in the Phase I/IIa combination study of BriaCell’s lead candidate, Bria-IMT™, with Incyte’s checkpoint inhibitor,

retifanlimab.

The additional clinical sites include the following:

1) Atlantic Health System, Morristown, New Jersey, and 2) Tranquil

Clinical Research, Webster, Texas.

advances preparatory work for new Bria-OTS™ breast cancer clinical trial

April 7, 2022, the Company announced that its novel off-the-shelf (“ OTS ”) personalized immunotherapy, Bria-OTS™,

is currently being manufactured at a cGMP facility and undergoing quality control testing for the potential upcoming clinical trial for

patients with advanced breast cancer.

Receives FDA Fast Track Approval for Targeted Breast Cancer Immunotherapy

April 13, 2022, the Company announced that the FDA has granted Fast Track status to BriaCell’s lead candidate, Bria-IMT™,

for the treatment of metastatic breast cancer (i.e.

breast cancer that has spread beyond the breast).

The Fast Track designation will

apply to patients with metastatic breast cancer.

BriaCell is developing Bria-IMT™ in combination with immune checkpoint inhibitors

in a clinical trial listed in ClinicalTrials.gov as NCT03328026.

BriaCell is currently enrolling and dosing advanced breast cancer patients

in its Phase I/IIa combination study of Bria-IMT™ with Incyte’s checkpoint inhibitor, retifanlimab under corporate collaboration

data on patient survival in this study was first presented at the San Antonio Breast Cancer Symposium in December 2021 and was over 12

months in spite of the patients being very heavily pre-treated having failed on average 9 prior regimens) compared with 7-10 months in

a study in 3rd line breast cancer patients (i.e.

those who failed 2 prior regimens for metastatic breast cancer) 1.

Other patient subsets

with possible survival benefit included those who match Bria-IMT™ at 1 or more HLA type and those with grade I (i.e.

well differentiated)

or grade II (i.e.

moderately differentiated) breast cancer.

Adds Additional Clinical Sites to Broaden Patient Access and Further Boost Enrollment

May 18, 2022, the Company announced that it has activated Hoag Memorial Hospital Presbyterian and re-engaged Sylvester Comprehensive

Cancer Center, part of the University of Miami Health System, as two additional clinical sites for the screening and enrollment of advanced

breast cancer patients in the Phase I/IIa combination study of BriaCell’s lead candidate, Bria-IMT™, with Incyte’s

checkpoint inhibitor, retifanlimab.

Anti-Cancer Technology Published in Leading Cancer Drug Discovery Journal

June 24, 2022, the Company announced the publication of novel scientific data and clinical data (previously reported) on BriaCell’s

lead candidate, Bria-IMT™.

The abstract of the paper was published on-line in Recent Patents on Anti-Cancer Drug Discovery, a publication

focused on research (where patents have been registered) in leading therapeutic areas, targets, and agents related to anti-cancer drug

The publication highlights BriaCell’s approach to developing novel cellular immunotherapies for cancer and the safety

and efficacy of Bria-IMT™ against advanced breast cancer in a prior clinical study through a potentially unique mechanism of action.

The full text of the article will be made available.

Enters Research Agreement to Identify Novel Targets for Cancer Treatment

June 28, 2022, the Company announced a research collaboration agreement with Harvard Medical School in support of a project led by Joan

Brugge, PhD, a faculty member.

The project aims to discover new targets that may lead to the development of novel anti-cancer treatments.

research collaboration will focus on the discovery and development of novel targets to enhance tumor cell responsiveness to chemotherapy

and immunotherapies in specific cancers including lung, head and neck, cervical, and bladder cancers.

The research team at Harvard Medical

School is led by Joan S.

Brugge, PhD, who is the Louise Foote Pfeiffer Professor of Cell Biology and Co-Director of the Ludwig Cancer

Company will have the option to negotiate a license to innovations owned by Harvard University that arise under the one-year collaboration.

The research agreement was coordinated by Harvard’s Office of Technology Development.

Partners with Waisman Biomanufacturing to Manufacture and Supply Prostate Cancer Immunotherapy

July 5, 2022, the Company announced a clinical-stage biotechnology company specializing in targeted immunotherapies for cancer, has entered

a manufacturing service agreement with Waisman Biomanufacturing at the University of Wisconsin–Madison (“ Waisman ”),

to manufacture Bria-Pros™, the Company’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.

the terms of the agreement, Waisman will be responsible for good manufacturing practice in the manufacturing of Bria-Pros™ for

anticipated use in clinical studies.

Waisman’s expert team will be working closely with the Company’s scientific and product

development teams to ensure timely production of Bria-Pros™ in compliance with applicable regulatory requirements by the FDA.

Secures License for a Promising Novel Anti-Cancer Agent

August 2, 2022, the Company 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.

The novel technology,

originally developed by Suzanne Ostrand-Rosenberg, PhD, Faculty at UMBC, and BriaCell’s scientific advisory board member, is entitled

“Soluble CD80 as a Therapeutic to Reverse Immune Suppression in Cancer Patients” (Patent No.

US 9,650,429 B2).

models, sCD80 has been shown to be safe and effective in stopping the tumor growth in animal models by potentially restoring natural

anti-tumor immunity.

Importantly, sCD80’s unique actions may involve both awakening and boosting the immune system to recognize

and destroy tumor cells.

the terms of the agreement, BriaCell gains the worldwide rights to develop and commercialize sCD80 as a therapeutic agent for the treatment

of cancer, while UMBC holds all rights, title and interest in the inventions and the patent, except for certain rights retained by the

United States Government.

BriaCell will pay 2% royalties to UMBC upon the commercialization of the product plus other development costs.

The licensing agreement was coordinated by UMBC.

BriaCell Partners with Caris Life Sciences®

to Expand Patient Outreach and Molecular Profiling

On September 14, 2022, the Company

signed an agreement with Caris Life Sciences ® (Caris), a leading molecular science and technology company actively developing and

delivering innovative solutions to revolutionize healthcare.

Under the terms of the agreement, Caris will help

BriaCell with efficient patient identification, accelerating enrollment for its current Phase I/II clinical trial in advanced metastatic

breast cancer of certain genetically defined subgroups.

The partnership between BriaCell and Caris leverages Caris’ Right-In-Time

(RIT) Clinical Trial Network, a group of over 495 oncology sites that are able to quickly identify and enroll eligible patients in biomarker-directed

clinical trials.

This service offers patients and physicians access to the most cutting-edge precision medicine in development.

Additionally,

through Caris’ comprehensive molecular profiling (Whole Exome and Whole Transcriptome Sequencing), Caris will perform tumor profiling

for the patients enrolled in the clinical trial.

BriaCell Announces New Clinical Trial Site to Bring

Novel Cancer Treatments to Advanced Breast Cancer Patients

On October 12, 2022, the Company

announced it has added Mayo Clinic, Jacksonville, Florida as a clinical site in the Phase I/II study of BriaCell’s lead candidate,

Bria-IMT™, with Incyte’s PD-1 inhibitor, retifanlimab, in advanced breast cancer.

BriaCell Announces Successful Completion of Phase

I Portion of Clinical Study in Advanced Breast Cancer;

Randomized Phase II Efficacy Evaluation Progressing

On October 21, 2022, the Company

announced the completion of the Phase I part of the clinical trial of its lead candidate, Bria-IMT™, in combination with Incyte’s

PD-1 inhibitor, retifanlimab, in advanced breast cancer.

The efficacy and survival data of the treated patients is being evaluated in

the Phase II part of the study which was recently awarded the FDA’s fast track designation.

Under an FDA approved protocol, another

arm has recently been added to the Phase II study to evaluate the effects of dosing schedules for patients in the study.

The Phase I portion of the trial,

with the primary goal of assessing safety and tolerability of the combination, enrolled 12 subjects who had previously failed at least

two prior lines of therapy, characterized as a difficult-to-treat patient population.

The combination treatment had a favorable safety

profile and appeared well-tolerated with no dose-limiting toxicities.

Progressing through the Phase

II part of the clinical trial, a randomized controlled design will be used to allow comparison of the effectiveness of the treatment regimens

between the two arms of the study with different dosing schedules.

BriaCell noted it is on schedule to meet with the

FDA later this year to discuss the design of a key registration study.

Plan of Arrangement

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

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.

lead drug discovery candidates for BriaPro includes:

Bria-TILsRx™:

Multi-Specific

Binding Reagents – Immunotherapy for Cancer:

being developed in collaboration with ImmunoPrecise Antibodies.

Small Molecule Program:

Protein Kinase C delta (PKCδ) Inhibitors being developed with Receptor AI.

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.

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.

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.

On May 9, 2023, the Company entered into a

Master Service and Technology Agreement (the “MST Agreement”) with Prevail InfoWorks, Inc.

(“InfoWorks”) pursuant

to which InfoWorks will provide clinical services and technologies for the Company’s upcoming pivotal study in advanced metastatic

breast cancer.

The Company has agreed to pay InfoWorks $5,379,945 upon signing of the MST Agreement and pay InfoWorks additional fees

upon the achievement of certain milestones.

On May 12, 2023, the Company entered into a stock purchase agreement (the “Prevail Partners Purchase Agreement”)

with Prevail Partners, LLC, an investment fund and affiliate of InfoWorks, pursuant to which the Company agreed to issue 463,408 common

shares for an aggregate purchase price of $4,000,000.

The funds received were used to pay amounts owed to InfoWorks under the MST Agreement.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business