LYON, France--(BUSINESS WIRE)--POXEL SA (Euronext: POXEL - FR0012432516), a clinical stage biopharmaceutical company developing innovative treatments for serious chronic diseases with metabolic pathophysiology, including non-alcoholic steatohepatitis (NASH) and rare metabolic disorders, today announced its results for the year ended December 31, 2021 and provided a corporate update.
“The year 2021 was a pivotal year in Poxel’s evolution, first noted by the marketing approval in June for Imeglimin in Japan, followed by commercialization since September under the name TWYMEEG®. This approval is strong validation of our R&D capabilities and the result of many years of effort by our team in close collaboration with our partner, Sumitomo Dainippon Pharma,” stated Thomas Kuhn, CEO of Poxel. “Secondly, Poxel initiated its strategic shift with a new emphasis on rare metabolic diseases, starting with ALD. We have made significant progress preparing for our Phase 2a Proof-of-Concept clinical studies for PXL065 and PXL770 in ALD. These studies, subject to additional funding, are planned to start in the middle of 2022, with results expected in early 2023. We are also extremely pleased that the FDA recently granted Fast Track status to PXL065 in ALD which confirms our strategic direction and has the potential to substantially accelerate the approval timeline for PXL065 in ALD.”
“In 2022, we look forward to sharing topline results of DESTINY-1, our Phase 2 study in NASH for PXL065, expected in the third quarter. We are actively pursuing a number of funding initiatives in parallel to extend our cash runway, prioritizing non-dilutive options. We are in advanced discussions with several parties and are confident that we will close a transaction in a reasonable timeframe to execute our strategic plan with the goal of bringing innovative treatments to patients with chronic serious metabolic diseases,” continued Thomas Kuhn.
Commercial Update
TWYMEEG® (Imeglimin)
- As of December 31, 2021, royalty revenue to Poxel based on TWYMEEG net sales in Japan under the Sumitomo Dainippon Pharma (“Sumitomo”) license agreement has been limited following TWYMEEG’s recent commercial launch on September 16, 2021. TWYMEEG’s initial commercial uptake has been impacted by prescribing restrictions for new products during the first year of sales and COVID-19 conditions. This has also impacted the frequency of physician visits and limited the significant market education efforts required for an innovative new product with a new mechanism of action.
- Sumitomo has made significant progress establishing high awareness of TWYMEEG amongst prescribing physicians, thanks to its comprehensive launch activities and ongoing promotional efforts. TWYMEEG has the potential to be used both in combination with other treatments, such as DPP4i’s, which are the most prescribed treatments for Japanese Type-2-Diabetes patients, and as monotherapy.Moreover, based on the Phase 3 TIMES program having shown robust efficacy with a favorable safety and tolerability profile, TWYMEEG offers potential for populations with limited treatment options, including elderly and patients with renal impairment. Sumitomo recently initiated a Phase 4 study targeting Type-2-Diabetes patients with chronic kidney diseases (CKD) 3b/4 / 5.
- In accordance with the Sumitomo license agreement, Poxel is entitled to receive escalating royalties of 8 - 18% on net sales of TWYMEEG and sales-based payments of up to JPY 26.5 billion (approximately EUR 200 million)1. In parallel, as part of the Merck Serono licensing agreement2, Poxel will pay Merck Serono a fixed 8% royalty based on the net sales of Imeglimin, independent of the level of sales. As a result, based on the current forecast, Poxel expects net royalties to be cash neutral through Sumitomo FY2022 (through March 2023). Once TWYMEEG achieves the next commercial threshold, the royalty rate will increase to double-digits and Poxel will retain all net royalties above 8%.
- Throughout 2021, Poxel and Sumitomo have continued to pursue strong patent protection for Imeglimin. The patent estate for TWYMEEG would extend to 2036 (including potential 5-year patent term extension), with other patent applications ongoing.
- In 2021, the Company conducted and completed a comprehensive evaluation of partnering options for the U.S. and Europe and does not expect to enter into a broad strategic partnership for these geographies in the near term. The Company is now considering opportunities to leverage the Imeglimin data package in specific territories, including those resulting from inbound interest.
-
Results from all three Phase 3 clinical trials of Imeglimin were published in the medical journals Diabetes Care and Diabetes Obesity and Metabolism:
- The TIMES 1 publication entitled: "Efficacy and safety of Imeglimin monotherapy vs. placebo in Japanese patients with Type 2 diabetes (TIMES 1) : A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Phase 3 Trial” was published in April 2021.
- The TIMES 2 publication entitled: “Long-term safety and efficacy of Imeglimin as monotherapy or in combination with existing antidiabetic agents in Japanese patients with type 2 diabetes (TIMES 2): A 52-week, open-label, multicentre phase 3 trial” was published in December 2021.
- The TIMES 3 publication entitled: “Efficacy and safety of Imeglimin add-on to insulin monotherapy in Japanese patients with type 2 diabetes (TIMES 3): A randomized, double-blind, placebo-controlled phase 3 trial with a 36-week open-label extension period” was published in January 2022.
Clinical Development Updates
NASH (PXL065 and PXL770)
- In September 2021, the PXL065 Phase 2 trial (DESTINY-1) in NASH completed enrollment with 123 noncirrhotic biopsy-proven NASH patients across multiple clinical sites in the US. Results from this 36-week, randomized, double-blind, placebo-controlled, parallel group, dose-ranging study designed to assess efficacy and safety are anticipated in Q3 2022. The goal of DESTINY-1 is to identify the optimal dose or doses of PXL065 to advance into a Phase 3 registration trial for the treatment of noncirrhotic biopsy-proven NASH patients.
- In November 2021, Poxel presented new clinical analysis on PXL065 DESTINY-1 screening data at the AASLD The Liver Meeting® 2021.
- PXL770, a first-in-class, oral direct adenosine monophosphate-activated protein kinase (AMPK) activator, has successfully completed a Phase 2a Proof-of-Concept trial for the treatment of NASH, which met its objectives. Future development of PXL770 in NASH will be assessed pending results from the PXL065 Phase 2 trial in NASH and the Phase 2a POC studies in ALD.
Rare metabolic diseases (PXL065 and PXL770)
- The Phase 2a clinical Proof-of-Concept (POC) biomarker program in X-linked adrenoleukodystrophy (ALD), subject to additional funding, is anticipated to begin midyear, followed by results in early 2023.
- In December 2021, Poxel announced the formation of its Scientific Advisory Board (SAB) for rare metabolic diseases as part of its strategy to increase its focus on rare diseases. The first meeting of this SAB included productive discussions that informed the design of the upcoming ALD POC Phase 2a studies and provided insights into pivotal trial concepts.
- Poxel participated in several scientific and patient advocacy conferences related to ALD and presented its programs, including the comprehensive preclinical pharmacological package, targeting this severe orphan neurometabolic disease with no approved therapies. This included presentations at three major advocacy organizations, Alex The Leukodystrophy Charity in the United Kingdom, United Leukodystrophy Foundation and ALD Connect in the U.S.
Early Stage Development
- During the year, Poxel pursued its evaluation of internal opportunities from its adenosine monophosphate-activated protein kinase (AMPK) activator platform and deuterated TZD platform and completed a series of studies, including a preclinical assessment of PXL770 and AMPK activation for an orphan kidney disease, autosomal dominant polycystic kidney disease (ADPKD), which demonstrated a robust effect to attenuate disease in established model systems. Additionally, the Company is conducting studies in other rare diseases including mitochondrial disorders.
Corporate Update
- In July 2021, Poxel announced a new strategic direction to focus its pipeline on high value, rare metabolic indications and NASH, with the goal of creating pipeline synergies, maximizing resources, and driving shareholder value. Rare metabolic indications represent the intersection of high unmet medical need, promising pre-clinical and clinical data, opinion leader enthusiasm, significant commercial opportunity, and attractive time horizons.
- In 2021, Poxel finalized a one year review and comprehensive evaluation of its existing Corporate Social Responsibility (CSR) actions. As a result, the Company has defined a solid CSR strategy supported by three pillars (social, governance and environmental) and will commit to measure, assess and communicate its progress over time, starting with the publication of its new CSR report which will be included in the 2021 Universal Registration Document. In order to enhance CSR as a corporate priority, Quentin Durand, Executive Vice President, Chief Legal Officer, has been appointed Head of CSR.
Significant Events after the Period
- In February 2022, the U.S. Food and Drug Administration (FDA) granted Fast Track status to PXL065 for ALD in patients with adrenomyeloneuropathy (AMN). Fast Track Designation (FTD) is awarded by FDA to investigational drugs which treat a serious or life-threatening condition, and which fill an unmet medical need. FDA notes that 'the purpose [of the Fast Track program] is to get important new drugs to the patient earlier’3.
Financial Statements for Full Year 2021 (IFRS Standards)
Income statement
EUR (in thousands) |
FY |
FY |
|
2021 12 months |
2020 12 months adjusted** |
Revenue |
13,397 |
6,806 |
Cost of sales |
(59) |
|
Gross margin |
13,339 |
6,806 |
Net research and development expenses* |
(25,174) |
(26,702) |
General and administrative expenses |
(10,627) |
(9,923) |
Operating income (loss) |
(22,463) |
(29,819) |
Financial income (expenses) |
(1,297) |
(1,975) |
Income tax |
(2) |
(36) |
Net income (loss) |
(23,763) |
(31,831) |
*Net of R&D tax credit and other subsidies.
**Change in accounting policies related to the application of IAS19.
The audit procedures are ongoing.
Poxel reported revenues of EUR 13.4 million for the year ended December 31, 2021, as compared to EUR 6.8 million during the corresponding period in 2020.
The revenues for 2021 include the following payments from Sumitomo Dainippon Pharma (“Sumitomo”) under the Sumitomo license agreement:
- JPY 1.75 billion (EUR 13.2 million) milestone payment for the approval of TWYMEEG in Japan on June 23, 2021, and
- JPY 7.5 million (EUR 58 thousand) of royalty revenue which represents 8% of TWYMEEG net sales in Japan.
Cost of sales amounted to EUR 58 thousand, corresponding to the 8% royalties on net sales of Imeglimin in Japan due to Merck Serono, as part of the Merck Serono license agreement.
R&D expenses totaled EUR 25.2 million in 2021, as compared to EUR 26.7 million in 2020. R&D expenses in 2021 primarily reflected the clinical costs incurred for the ongoing PXL065 Phase 2 DESTINY-1 trial.
R&D costs are net of the R&D Tax Credit (CIR) and other subsidies that resulted in income of EUR 2.3 million in 2021, as compared to EUR 2.5 million in 2020.
General and administrative expenses totaled EUR 10.6 million in 2021, as compared to EUR 9.9 million in 2020.
The financial loss amounted to EUR 1.3 million in 2021, as compared to a loss of EUR 2.0 million in 2020.
The net result for the financial period ending December 31, 2021 was a net loss of EUR 23.8 million, as compared to a net loss of EUR 31.8 million in 2020.
Cash
As of December 31, 2021, total cash and cash equivalents amounted to EUR 32.3 million (USD 36.6 million), as compared to EUR 40.2 million (USD 49.4 million) as of December 31, 2020. Net financial debt (excluding IFRS16 impacts and derivative instruments) amounted to EUR 2.6 million at December 31, 2021, compared to EUR (17.2) million at December 31, 2020.
Based on:
- the cash position at December 31, 2021,
- the current development plan of the Company including 1) the completion of its ongoing Phase 2 NASH trial for PXL065 (DESTINY-1) ) but 2) excluding the two identical Phase 2a clinical proof-of-concept (POC) biomarker studies for PXL065 and PXL770 in adrenomyeloneuropathy (AMN),
- the cash forecast for the year 2022 approved by the Board of Directors of the Company, that 1) does not include, as a conservative approach, any net sales from Imeglimin in Japan and 2) includes an amount of EUR 4,813 thousands for the repayments of the loan with IPF partners until December 2022, and
- a strict control of its operating expenses,
the Company expects that its resources will be sufficient to fund its operations and capital expenditure requirements through at least December 31, 2022, representing 12 months from the reporting date. However, the Company is subject to certain financial covenants4 related to its debt with IPF Partners which could be potentially breached in Q3 2022. This situation could lead the Company’s auditors to issue an audit opinion which would include a paragraph related to the going concern.
The Company is actively pursuing various financing options which would extend its cash runway and avoid any breach of financial covenants through at least 12 months from the reporting date. These financing options include dilutive and non-dilutive sources, as well as discussions with IPF partners, and the Company reasonably expects that at least one of the pursued options would be completed before Q3 2022. As a consequence, the Company’s 2021 financials are presented on a going concern basis.
Planned Presentations and Participation at the Following Upcoming Events
- Annual Meeting of the Japanese Diabetes Society, Kobe, Japan, May 12-14
- European Renal Association Congress, Paris, France, May 19-22
- Global NASH Congress, London, UK, May 26-27
- Jefferies Global Healthcare Conference, New York, NY, June 8-10
- JMP Securities 2022 Life Sciences Conference, New York, NY, June 15-16
Next Financial Press Release: First Quarter 2022 Financial Update, May 17, 2022
About Poxel SA
Poxel is a clinical stage biopharmaceutical company developing innovative treatments for chronic serious diseases with metabolic pathophysiology, including non-alcoholic steatohepatitis (NASH) and rare disorders. Poxel has clinical and earlier-stage programs from its adenosine monophosphate-activated protein kinase (AMPK) activator and deuterated TZD platforms targeting chronic and rare metabolic diseases. For the treatment of NASH, PXL065 (deuterium-stabilized R-pioglitazone) is in a streamlined Phase 2 trial (DESTINY-1). PXL770, a first-in-class direct AMPK activator, has successfully completed a Phase 2a proof-of-concept trial for the treatment of NASH, which met its objectives. For the rare inherited metabolic disorder, adrenoleukodystrophy (ALD), the company intends to initiate Phase 2a proof of concept studies with PXL065 and PXL770 in patients with adrenomyeloneuropathy (AMN). TWYMEEG® (Imeglimin), Poxel’s first-in-class lead product that targets mitochondrial dysfunction, has been approved and launched for the treatment of type 2 diabetes in Japan. Poxel expects to receive royalties and sales-based payments from Sumitomo Dainippon Pharma. Poxel has a strategic partnership with Sumitomo Dainippon Pharma for Imeglimin in Japan, China, South Korea, Taiwan and nine other Southeast Asian countries. The Company intends to generate further growth through strategic partnerships and pipeline development. Listed on Euronext Paris, Poxel is headquartered in Lyon, France, and has subsidiaries in Boston, MA, and Tokyo, Japan.
For more information, please visit: www.poxelpharma.com
All statements other than statements of historical fact included in this press release about future events are subject to (i) change without notice and (ii) factors beyond the Company’s control. These statements may include, without limitation, any statements preceded by, followed by or including words such as “target,” “believe,” “expect,” “aim,” “intend,” “may,” “anticipate,” “estimate,” “plan,” “project,” “will,” “can have,” “likely,” “should,” “would,” “could” and other words and terms of similar meaning or the negative thereof. Forward-looking statements are subject to inherent risks and uncertainties beyond the Company’s control that could cause the Company’s actual results or performance to be materially different from the expected results or performance expressed or implied by such forward-looking statements. The Company does not endorse or is not otherwise responsible for the content of external hyperlinks referred to in this press release.
1 Converted at the exchange rate at the date of the agreement (30 Oct 2017).
2 As described in the “2.3.1. Merck Serono Agreement” section of the Poxel 2020 Document d’Enregistrement Universel.
3 https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/fast-track.
4 Under these financial covenants the Company should maintain minimum cash position of the higher of i) ten million euros and ii) the sum of the consolidated debt service of the Company plus the amount of cash required to be spent by the Company as part of its operations, in each case for the following 6-month period.
