Resverlogix : MD&A Q1 2023

MANAGEMENT'S DISCUSSION & ANALYSIS - Q1 2023 (March 31, 2023)

This Management's Discussion and Analysis ("MD&A") of Resverlogix Corp.'s operations and financial position should be read in conjunction with the unaudited condensed interim consolidated financial statements and the notes thereto for the three months ended March 31, 2023 and 2022, and the audited consolidated financial statements and the notes thereto and the Management's Discussion and Analysis for the years ended December 31, 2022 and 2021. This MD&A is dated May 11, 2023. Our financial statements have been prepared by management in accordance with International Financial Reporting Standards ("IFRS") and comprise Resverlogix Corp. ("Resverlogix" or the "Company") and its wholly-owned subsidiary Resverlogix Inc. (together referred to as the "Group"). All amounts in the following MD&A are stated in US dollars unless otherwise stated. References to "we", "us" or "our" mean Resverlogix Corp. and its subsidiary unless the context otherwise requires.

Cautionary Statement Regarding Forward-Looking Information

This MD&A contains forward-looking information within the meaning of applicable Canadian securities legislation. Forward-looking information is often, but not always, identified by the use of words such as "believes", "anticipates", "plans", "intends", "will", "should", "expects", "continue", "estimate", "forecasts" and other similar expressions. In particular, this MD&A includes forward-looking information related to:

• aim to commercialize or license to a pharmaceutical partner our products for the treatment of unmet medical needs related to prevention of: major adverse cardiovascular events in patients with diabetes mellitus and chronic kidney disease; post COVID- 19 conditions and additional indications;
• aim to carry out trials on our products for the treatment of unmet medical needs related to major adverse cardiovascular events in patients with higher risk such as acute coronary syndrome, diabetes mellitus and chronic kidney disease, post COVID-19 conditions and additional indications, and the timing of such trials;
• plans related to our post COVID-19 conditions, cardiovascular disease and other programs and the planning and design of clinical trials as part of each of these programs;
• expectations relating to the timing of significant clinical trial milestones;
• the function and effectiveness of apabetalone, also referred to as RVX-208;
• the development of new compounds and the potential impact of these compounds on multiple diseases;
• aim to obtain regulatory approval for our products;
• expectations with respect to the cost of clinical trials and commercialization of our products;
• projected competitive conditions with respect to our products;
• anticipated sources of revenue and the estimated market for our products;
• expectations regarding the protection of our intellectual property;
• business strategy;
• intentions with respect to dividends; and
• potential milestone payments and royalties pursuant to the license agreements with Shenzhen Hepalink Pharmaceutical Co., Ltd. ("Hepalink") and Medison Pharma Ltd.

Readers are cautioned that our expectations, beliefs, projections, and assumptions used in preparation of such information, although considered reasonable at the time of preparation, may prove to be wrong, and as such, undue reliance should not be placed on forward-looking statements. With respect to forward-looking statements contained in this MD&A, we have made key assumptions including:

• general business and economic conditions;
• interest rates;

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• the timing of the receipt of regulatory and governmental approvals for research and development projects;
• the availability of financing for research and development projects, or the availability of financing on reasonable terms;
• the ability to refinance existing indebtedness on reasonable terms upon maturity;
• the impact of changes in Canadian dollar-US dollar and other foreign exchange rates on our costs and results;
• market competition;
• our ability to attract and retain skilled staff; and
• ongoing relations with employees and with business partners.

Our actual results, events or developments could be materially different from those expressed or implied by these forward-looking statements. We can give no assurance that any of the events or expectations will occur or be realized. By their nature, forward-looking statements are subject to numerous known and unknown risks and uncertainties including but not limited to:

• risks related to the early stage of our products;
• uncertainties related to clinical trials and product development;
• uncertainties related to current economic conditions;
• risks related to rapid technological change;
• uncertainties related to forecasts and timing of clinical trials and regulatory approval;
• competition in the market for therapeutic products to treat cardiovascular disease, neurodegenerative diseases, diabetes mellitus and other high risk vascular diseases;
• risks related to potential product liability claims;
• availability of additional financing and access to capital for research and development, clinical trials, and regulatory approval;
• market acceptance and commercialization of our products;
• the availability and supply of raw materials, including supplies of sufficient active pharmaceutical ingredients for large clinical trials and future commercial production;
• risks related to the effective management of our growth;
• potential reliance on partnering agreements to provide support for discovery and development efforts, and on corporate sponsors, pharmaceutical companies, and others to successfully develop and commercialize our technology;
• the willingness of health care insurers and other organizations to pay for our products;
• risks related to our reliance on key personnel;
• risks related to the regulatory approval process for the manufacture and sale of non-therapeutic and human therapeutic products; and
• our ability to secure and protect our intellectual property, and to operate without infringing on the proprietary rights of others or having third parties circumvent the rights owned or licensed by us.

You should also carefully consider the matters discussed under "Risk Factors" in our Annual Information Form and other documents we file from time to time with securities authorities, which are available through SEDAR at www.sedar.com. Additionally, risks and uncertainties are discussed on page 14 of this MD&A.

The forward-looking statements contained in this MD&A are expressly qualified by this cautionary statement. We disclaim any intention and have no obligation or responsibility, except as required by law, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Going Concern

Our success is dependent on the continuation of our research and development activities, progressing the core technologies through clinical trials to commercialization or a strategic partnership, and our ability to obtain additional financing. It is not possible to predict the outcome of future research and development programs, our ability to fund these programs in the future, or to secure a strategic partnership, or the commercialization of products. To date, we have not generated any product revenue. We have incurred significant losses to date, and with no assumption of revenues, we are dependent on our ability to raise additional financial capital by continuing to demonstrate the successful progression of our research and development activities if we are to remain as a going concern.

As at March 31, 2023, we had $3 thousand of cash. We need to raise additional capital to fund research, development and corporate activities over the next year or we may be forced to cease operations. As at March 31, 2023, we were committed to pay $14.6 million of current trade and other payables, $1.4 million for research and development over the next twelve months, and $0.3 million of lease

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liabilities over the next twelve months. Furthermore, our $6.0 million secured convertible debenture with Hepalink is due on May 13, 2024. As at March 31, 2023, the Group is also party to a commercialization partnership; the parties have mutually agreed to temporarily pause services and the Group is not obligated as at March 31, 2023 to incur pre-commercialization costs over the next twelve months. The parties may or may not resume services over the next twelve months.

Our cash as at March 31, 2023 is not sufficient to fund our contractual commitments or our planned business operations over the next year. Therefore, we will have to raise additional capital to fund our contractual commitments and our planned business operations. We continue to pursue and/or examine several sources of additional capital including co-development, licensing, rights or other partnering arrangements, procurement arrangements, private placements and/or public offerings (equity and/or debt). However, there is no assurance that any of these measures will be successfully completed.

The Company will also require additional capital to fund research, development, and corporate activities beyond the next year. The Company will continue to explore alternatives to generate additional cash including raising additional equity and/or debt and/or partnering; however, there is no assurance that these initiatives will be successful.

These conditions result in a material uncertainty which may cast significant doubt on our ability to continue as a going concern. If we are not able to raise capital, we may be forced to cease operations.

Overview

Company Overview

Resverlogix is a late-stage clinical biotechnology company dedicated to improving the lives of patients with chronic illnesses. We focus on the development of a new class of therapeutics, bromodomain and extraterminal domain ("BET") protein inhibitors. BET proteins play a central role in epigenetics and enable the transcription of disease-causing genes. Our small-molecule BET inhibitors are designed to exploit this central epigenetic role to regulate gene expression and tackle the root causes of chronic diseases.

Due to the extensive role of BET proteins in many cell types throughout the human body, BET inhibitors can simultaneously benefit multiple pathological processes. Several complex chronic conditions, including cardiovascular disease ("CVD"), diabetes mellitus ("DM"), chronic kidney disease ("CKD"), vascular cognitive impairment ("VCI"), non-alcoholic fatty liver disease ("NAFLD"), post COVID- 19 conditions ("PCC"), and pulmonary arterial hypertension ("PAH), share common underlying biological processes that drive disease progression and are associated with negative patient outcomes. Combinations of inflammation, calcification, fibrosis, dyslipidemia, metabolism, and cell proliferation contribute to these conditions, and many others.

Most conventional pharmaceuticals target single proteins, based on the expectation of interrupting a critical step in the development of a disease. This has been the template for decades: one disease, one target, one compound. While this this approach can be very effective in treating diseases that result from the dysregulation of a single gene or protein, we believe it is limited in its ability to combat diseases with many contributing factors - such as CVD, CKD, and DM. By aiming upstream of typical pharmaceuticals, and targeting gene transcription, we can effectively regulate expression of entire signaling pathways. Our goal is to define a new drug development template: one compound, multiple signaling pathways, shared by multiple complex diseases.

Apabetalone (RVX-208)

Apabetalone, the first BET inhibitor in advanced clinical trials outside of oncology, is our lead compound and a selective inhibitor of the second bromodomain (BD2) on BET proteins. With robust intellectual property protection (extending to 2040), over 40 peer- reviewed scientific publications, 4200 patient-years of Food & Drug Administration ("FDA") reviewed safety data, detailed proteomic and transcriptomic analysis, as well as FDA breakthrough therapy designation, apabetalone is a thoroughly characterized and de- risked asset.

The largest study of apabetalone to date, BETonMACE, was a Phase 3, multi-centered,placebo-controlled, clinical trial, investigating apabetalone for the secondary prevention of major adverse cardiac events ("MACE"), in a high-risk population. Trial participants treated with apabetalone saw reduced incidence of MACE (10.9%), a composite endpoint of cardiovascular ("CV") death, non-fatal myocardial infarction ("MI"), and stroke, compared to the patients receiving a placebo (12.4%)1. The cardioprotective benefit of apabetalone was more pronounced in the prespecified subgroup of trial participants with CKD comorbidity, where apabetalone treatment was associated with a 50% hazard reduction in MACE2. Apabetalone also significantly reduced the hazard of hospitalization for congestive heart failure ("CHF") 3, a key secondary endpoint in the trial. Patients receiving apabetalone saw a 41% hazard reduction in first occurrence of hospitalization for CHF compared to those receiving standard of care treatment alone.

1. https://jamanetwork.com/journals/jama/fullarticle/2763951
2. https://journals.lww.com/cjasn/Abstract/2021/05000/Effect_of_Apabetalone_on_Cardiovascular_Events_in.9.aspx
3. https://cardiab.biomedcentral.com/articles/10.1186/s12933-020-01199-x

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Another significant finding that emerged from BETonMACE is the potentially synergistic benefit seen in trial participants who were administered sodium-glucosecotransporter-2 ("SGLT2") inhibitors concomitantly with apabetalone. Among patients receiving SGLT2 inhibitors a 65% hazard reduction in a composite of MACE and hospitalization for CHF was observed in those treated with apabetalone compared to placebo. This finding, along with other benefits seen in this group, contributed to filing three new patents related to the combination of SGLT2 inhibitors and BET inhibitor for the treatment of CVD, type 2 DM, and CKD.

Development stage overview for apabetalone in targeted clinical indications

Following the outcomes of BETonMACE, the FDA granted breakthrough therapy designation for apabetalone in combination with top standard of care, including high-intensity statins, for the secondary prevention of MACE in patients with type 2 DM and recent acute coronary syndrome. According to the FDA, this designation is intended to expedite the development and review of new drugs to address the unmet medical need in the treatment of serious or life-threatening conditions. As a result, apabetalone is eligible for intensive guidance and expedited review of clinical trial design and protocols along with planning to accelerate the manufacturing development strategy of the drug.

Through numerous clinical studies, apabetalone has established a strong track record of clinical safety and tolerability in multiple patient populations. Combined, over 1,800 patients have received apabetalone, and more than 4,200 patient-years of safety data has been accumulated and analysed for increased risk of adverse events and off-target effects. Apabetalone is well tolerated and has an adverse event profile that compares favourably to placebo controls. Selectively targeting BD2 is an important contributor to apabetalone's clinical safety, and a key distinguishing feature from other BET inhibitors, many of which are non-selective.Pan-BET inhibitors - which bind both bromodomains equally - have been found to disrupt the structure of chromatin and alter the fundamental functions of cells, potentially leading to cell death. BD2-selective inhibitors, on the other hand, are able to inhibit gene transcription while maintaining chromatin structure and cell viability.

Highlights

Clinical Development of Apabetalone

Cardiovascular Disease

Design and planning activity for BETonMACE2, a planned registration-enabling study of apabetalone in high-risk CVD patients with type 2 DM, was completed throughout 2022. Apabetalone's breakthrough therapy designation has enabled us to work closely with the FDA and receive timely feedback and guidance on the BETonMACE2 study protocol. Trial design has been guided by key findings from BETonMACE, including the strong positive impact of apabetalone on reducing CHF hospitalizations, its cardioprotective benefit in CKD patients, and the potential synergy with SGLT2 inhibitors. BETonMACE's primary endpoint, a composite of MI, stroke, and cardiovascular death, will be expanded to included hospitalizations due to CHF. The populations that experienced the most benefit from apabetalone in BETonMACE will be expanded for the upcoming trial. All patients are expected to receive SGLT2 inhibitor alongside the study drug, and the target proportion of CKD patients is anticipated to be significantly higher than it was for BETonMACE. BETonMACE2 is also expected to enroll more patients than BETonMACE, improving the likelihood of statistically significant findings. We believe these study parameters will best demonstrate apabetalone's benefit in treating cardiovascular disease. Subject to regulatory approval and securing financing, BETonMACE2 is expected to begin recruiting patients in 2024.

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Post COVID-19 Conditions

Following the conclusion of our Phase 2 study (NCT04894266), Resverlogix was granted a Type C meeting with the FDA to discuss an updated protocol for evaluating apabetalone in COVID-19 and a roadmap towards registration. Based on guidance from this meeting and the compelling opportunity for apabetalone to benefit patients, we announced that future development of apabetalone for COVID- 19 will focus on the treatment of Post COVID-19 Conditions ("PCC"), colloquially known as long-COVID. The US Centers for Disease Control and Prevention ("CDC") estimates4 that as many as one-in-three adults will experience PCC symptoms following COVID-19 infection. A growing body of evidence also highlights long-term risk of negative cardiovascular outcomes in COVID-19 survivors5. We believe apabetalone is well positioned to treat PCC and reduce cardiovascular risks in high-risk patients. Planning for a Phase 2/3 trial of apabetalone in PCC is underway and expected to be completed in 2023 or 2024, pending all necessary regulatory approval and securing financing.

Pulmonary Arterial Hypertension

In March 2022, results of our pilot study of apabetalone in PAH, APPRoAcH-p, were published in the prestigious American Journal of Respiratory and Critical Care Medicine6. The article highlighted improvements in key study endpoints, including pulmonary vascular resistance, stroke volume, and cardiac output, among apabetalone-treated trial participants. The encouraging results of this study pave the way for the larger multi-centeredAPPRoAcH-2 trial, in collaboration with researchers at the Quebec Heart and Lung Institute, Laval University, who led the pilot study.

Publications and Presentations

As leaders in the field of epigenetic therapeutics, we believe it is our responsibility to participate in the scientific community and publish our findings in peer-reviewed scientific journals, whenever possible. In 2022, we published several articles on our pre-clinical and clinical work. In June we published a major breakthrough in the understanding of BD2-selective BET inhibitors. A new role for BET protein BRD4 was discovered, in maintaining the structure of chromatin (a compact, densely coiled structure made up of DNA and proteins, and found in the nucleus of our cells). For years it has been understood that both BD2-selective and non-selective (pan) BET inhibitors can both interrupt gene transcription by preventing the formation of transcription complexes at the site of certain genes. However, prior to this research, it was not understood that BD2-seletive BET inhibitors prevent transcription while maintaining chromatin structure, while pan-BET inhibitors do not. This finding provides a potential mechanism for the important differences in clinical safety outcomes observed between BD2-selective and non-selective BET inhibitors and highlights the safety of BD2-selective inhibitors like apabetalone.

Additional articles highlighting apabetalone's potential beneficial impact on Fabry's disease, NAFLD, and CVD7 were published in 2022. Fabry disease is a genetic disorder that affects lipid metabolism, resulting in systemic inflammation that contributes to life-threatening consequences in multiple organs - such as the heart and kidneys. Using immune cells donated by Fabry disease patients, our team demonstrated that apabetalone treatment alleviates inflammatory processes and oxidative stress. This finding suggests a potential role for apabetalone in the treatment of Fabry's disease. Analysis of BETonMACE clinical data, using a validated measure of NAFLD fibrosis score found that apabetalone treatment was associated with reduced incidence of MACE and CHF in NAFLD patients. NAFLD is common among type 2 DM patients and is linked to higher cardiovascular risk. Finally, an article published in early 2023 further detailed the cardiometabolic effects of apabetalone. Using a diet-induced obesity mouse model, our team replicated the pro- inflammatory signaling seen in obese patients, who are at high risk of type 2 DM and CVD. The research demonstrated that apabetalone counters inflammatory signaling, providing mechanistic insight into how it may reduce CVD risk in obese patients.

Members of our R&D and clinical development teams participated in participated in leading scientific conferences during 2022, including American Heart Association Scientific Sessions, American College of Cardiology Scientific Sessions, European Society of Cardiology Congress, and Clinical Trials on Alzheimer's Disease Congress. These articles and presentations not only showcase apabetalone to the global scientific community and allow us to connect with thought leaders in the space, but also publicizes concrete, peer-reviewed evidence of apabetalone's safety and efficacy. Our comprehensive body of evidence, and detailed mechanistic understanding of apabetalone, guides our clinical development and lends credibility in our discussions with potential partners.

1. https://www.cdc.gov/nchs/covid19/pulse/long-covid.htm
2. https://www.nature.com/articles/s41591-022-01689-3
3. https://www.atsjournals.org/doi/abs/10.1164/rccm.202109-2182LE
4. https://www.resverlogix.com/science-and-programs/publications

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