Hyloris Pharmaceuticals : 2023 Half Year Result - English

2023

Half-year Report

Reinventing existing medications

This report is prepared in accordance with article 13 of the Belgian Royal Decree of November 14, 2007. Hyloris publishes its Interim Financial Report in English and French. In the event of differences of interpretation between the English and the French versions of the Report, the original English version will prevail.

BUSINESS PERFORMANCE REVIEW

Key Highlights and Year-to-Date events

COMMERCIAL VALUE DRIVERS

Maxigesic® IV is a novel, unique combination, intravenous formulation for the treatment of post-operative pain and is currently licensed to partners covering over 100 countries across the globe.

The number of countries in which Maxigesic® IV has been approved has increased to more than 40. So far, launches have occurred in around 20 countries.

A potential approval date for the US market was set for 17 October 2023 by the U.S. Food & Drug Administration. The U.S. regulatory body confirmed that it had received a complete response in relation to the additional data on E&L (extractables and leachables) it had requested in July 2022.

Maxigesic® IV aims to provide an alternative, non-opioid treatment option for post-operative pain. In the United States, chronic opioid usage in patients following surgery averages around 9%, ranging from 4% to 24% among various specialties1. Drug overdoses involving opioids resulted in over 80.000 deaths in the U.S. in 20212. Patients who experienced an opioid overdose accounted for nearly $2 billion in annual hospital costs3.

On the condition of FDA approval, sales of Maxigesic® IV could start soon, with an exclusive license and distribution agreement already signed between Hyloris' partner AFT Pharmaceuticals and Hikma Pharmaceuticals, a leading supplier of complex, injectable hospital products in the U.S.

Under the terms of the development collaboration agreement between Hyloris and AFT, Hyloris is eligible to receive a share on any product-related revenues, such as license fees, royalties, milestone payments, received by AFT.

Subject to market approval by the FDA and the first U.S. sales, Hyloris will be be entitled to to a milestone of approximately $2 million as revenue.

Sotalol IV is a novel, patented, intravenous formulation of Sotalol for the treatment of atrial fibrillation, and life-threatening ventricular arrhythmias developed for the US. Sotalol IV allows to significantly reduce the length of hospital stay and potentially the overall cost of care potentially improving patient outcomes.

Hyloris is taking further steps to capture more of the growth potential in the future. In addition, Hyloris will capture a larger share of the product sales in the second half of the year as the royalty percentages are attributed to the Company on a step-up basis.

COMMERCIAL ROLL-OUT PREPARATION

Out-licensing agreements were signed for Tranexamic Acid RTU in early 2023, covering an important European country and a major Southeast Asian country, with a combined population of over 60 million people. Earlier agreements have been signed in 2021 for Australia, New-Zealand and Canada. Regulatory submissions in the partnered territories are in progress, and additional out-licensing agreements are expected going forward.

1. https://pubmed.ncbi.nlm.nih.gov/27163960/
2. Data Overview | Opioids | CDC
3. Premier | Opioid Overdoses Costing U.S. Hospitals an Estimated $11… (premierinc.com)

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Hyloris - 2023 Half-Year Financial Report

For product candidates which Hyloris intends to out-license, the strategic goal is to capture a substantial part of the net product margin realized by our commercial partners. The Company aims to achieve this by partnering these assets close to regulatory submission, except in countries where additional local clinical trials are required. In general, we will prioritize in-market product sales or profit-based participation over (upfront) milestone payments.

Cardiovascular portfolio

Hyloris is actively analyzing different go-to-market strategies to bring its range of cardiovascular product candidates to the U.S healthcare market in the most efficient way.

The strategic grouping of submission dates targeted by Hyloris makes 2025 a pivotal year for the Company, with several launches anticipated or in in preparation for the U.S. market by that year. These product candidates will be promoted primarily to electrophysiologists, a subset of cardiologists in hospitals.

Other value-added product candidates

With a growing portfolio and multiple product candidates progressing towards commercialization, the Company intends to sign partnerships with leading companies in their respective territories.

PIPELINE EXPANSION

The business development team applies its knowledge of established products and real-world data in the search for solutions to underserved medical needs. Inhouse knowhow is supplemented by leveraging dialogues with healthcare professionals, patient groups, payors and partners as well as our extensive sourcing network and R&D capabilities. We aim to create value by expanding our portfolio to 30 assets before 2025, and expect to accelerate pipeline expansion in the coming months.

In January 2023, Hyloris in-licensedHY-088, a product candidate targeting hypophosphatemia, a serious condition causing patients to have low level of phosphate in the blood. While mild hypophosphatemia is common and many patients are asymptomatic, severe hypophosphatemia can be life-threatening and requires medical treatment. Treatment protocols for patients deficient in phosphate are well-established and have proven useful in other situations of bone mineral imbalance, but in most countries no approved oral drugs exist.

By definition, the compounded drugs currently administered to patients have not been submitted for regulatory scrutiny regarding safety, efficacy and quality. Hyloris intends to achieve market access with an approved treatment in European countries.

R&D UPDATE & OUTLOOK

Swift & steady progress was made in the first half of 2023 to bring 14 repurposed and reformulated product candidates closer to patients in need, as well as 3 high barrier generics.

Our new and improved R&D lab is now operational at Légiapark in Liège (Belgium), the life sciences hub where Hyloris moved its head office at the end of 2022. Expanded R&D facilities and expertise will allow the Company to perform drug formulation and analytical activities in-house for its growing pipeline, further streamlining processes and more effectively deploying internal resources.

A non-exhaustive list of R&D achievements as well as selected milestones can be found below.

Cardiovascular portfolio

Progress has been made on all cardiovascular assets in the first half of 2023.

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Hyloris - 2023 Half-Year Financial Report

1. For Dofetilide IV, the results of the pivotal clinical study, allowing regulatory submission, are expected by the summer of 2024. Additional U.S. patent applications have been submitted. Dofetilide IV aims to reduce hospitalization stays and related risks and costs. Currently, Dofetilide is only available as an oral capsule, and Dofetilide formulated as an IV could be used as an initial loading dose with subsequent oral Dofetilide dosing to reduce the time to reach steady state and

hospital discharge.

1. Metolazone IV: The process of manufacturing the final registration batches is currently in progress, with stability testing expected to be initiated as soon as October 2023. The pivotal clinical trial is currently in preparation and an additional U.S. patent application has been submitted.
   Metolazone tablets are used in patients with congestive heart failure, the most rapidly growing cardiovascular condition globally and the leading cause of hospitalization. The potential benefits of Metolazone IV include accelerating onset of action, allowing simultaneous administration with furosemide IV (the most frequently used intravenous hospital diuretic), and improving drug absorption for patients with concomitant gastrointestinal oedema. The intravenous formulation

will also allow drug administration in patients who are too ill to receive oral medications or who are unconscious.

1. Aspirin IV: The transfer to a new contract manufacturing organization (CMO), required following a strategic review, has been successfully concluded. Discussions with the FDA on the drug development program are ongoing.

Aspirin IV is an intravenous formulation of acetylsalicylic acid (aspirin) targeting Acute Coronary Syndrome (ACS). When ACS occurs, fast diagnosis and treatment is crucial and potentially lifesaving.

1. HY-074: Regulatory submission for the U.S. market is expected shortly after submissions related to the other cardiovascular assets mentioned in this list. For HY-074, Hyloris is exploring additional indications outside of the cardiovascular space.
   HY-074 is an IV formulation of a current standard of care treatment significantly reducing risk of death in ACS patients. HY-074 aims to offer faster onset of action, more convenient administration (more notable in patients who are nauseated or unconscious) and dosage control.

Other value-added product candidates

Notable points of progress for our these product candidates are described below. Other product candidates have advanced in line with the timelines previously indicated.

1. AlenuraTM : At the start of the summer, the first patients entered a 4-arm study which is part of an ambitious adaptive phase 2 program. The 4-arm trial is currently targeting to enroll 120 patients across multiple sites in the U.S. Each subject will receive a single blinded dose of Alenura™, placebo, lidocaine, or heparin by random assignment.
   AlenuraTM is being developed as a ready-to-use instillation to be administered intra-vesicularly. The product candidate targets acute pain flares in patients with IC/BPS, which affects at least 6

million people in the US alone.

1. HY-083: A Phase 1 study was conducted demonstrating no systemic exposure could be detected following intranasal administration of the molecule using a nasal spray.

HY-083 targets idiopathic rhinitis, a medical disorder characterized by a collection of nasal symptoms that resemble nasal allergies and hay fever (allergic rhinitis) but are not caused by a known cause like allergens or infectious triggers.

1. Tranexamic Acid Oral Suspension: FDA agreement to proceed with the Phase 3 study was obtained, with the enrolment of the first patient expected in September 2023.
   TXA oral mouth rinse aims to reduce oral bleeding in patients undergoing dental procedures.

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Hyloris - 2023 Half-Year Financial Report