On October 10, 2024 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that overcome tumor immune evasion and drug resistance, reported it has been selected for a poster presentation at the 36th European Organization for Research and Treatment of Cancer, National Cancer Institute, American Association for Cancer Research (AACR) (Free AACR Whitepaper) (EORTC-NCI-AACR) (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics (the "Triple Meeting") held October 23-25, 2024 in Barcelona, Spain (Press release, Purple Biotech, OCT 10, 2024, View Source;id=322854&p=2344395&I=1206939-c7Z3G6f3m8 [SID1234647146]).

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Purple Biotech’s poster titled "CAPTN-3: A novel platform of conditionally activated T cell and NK cell engagers" (Abstract # 450, poster board number: PB438) will be presented by Dr. Hadas Reuveni, VP R&D of Purple Biotech, during a ‘New therapies in immuno oncology’ poster session on Friday, 25 October 2024.

CAPTN-3 is a First-in-class platform of conditionally activated tri-specific antibodies engaging both T cells and NK cells with the tumor to create an immune synapse with enhanced anti-tumor efficacy. The NK engager arm (aNKG2A) of our lead compound also acts as a checkpoint inhibitor for both NK cells and highly cytotoxic T cell subsets, unleashing both innate and adaptive immune subsets against the tumor.

Purple Biotech’s lead CAPTN-3 platform candidate, IM1240, targets 5T4 as a tumor associated antigen (TAA), which is overexpressed in a variety of solid tumors and is correlated with advanced disease, increased invasiveness, and poor clinical outcome. 5T4, also known as trophoblast glycoprotein (TPBG), is an oncofetal surface protein that is not found on adult healthy tissues but is abnormally expressed in several cancer types. This specific expression pattern as well as the correlation with poor prognosis in different cancer diseases such as lung, gastric, head and neck and other cancers makes it an ideal TAA for various therapeutic approaches.

On October 10, 2024 XENOTHERA, a Nantes-based biotech developing innovative treatments using multi-specific polyclonal glyco-humanized antibodies (GH-pAb), reported the recruitment of the first patient in its new clinical trial in onco-hematology. PALT1 is a multicenter phase I/II trial evaluating the safety and efficacy of its antibody directed against tumoral T-cells in patients with relapsed/refractory PTCL (NCT 06495723) (Press release, Xenothera, OCT 10, 2024, View Source [SID1234647145]). The PALT1 trial started at the beginning of July in five French centers.

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Meanwhile, the company received orphan drug designation (ODD) for this antibody in PTCL from the European Medicines Agency (EMA), in addition to the ODD already granted by the Food and Drug Administration (FDA).

Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin’s lymphomas for which there is a great medical need. PTCL are aggressive hematological tumors with a poor prognosis. Patients are generally treated with CHOP chemotherapy as first line, which unfortunately has limited efficacy, like other treatments, which response rate is usually less than 30%.

XENOTHERA’s antibody is derived from its platform of multi-specific glyco-humanized antibodies. In preclinical studies, it recognizes most PTCL, is more effective than CHOP on T lymphoma cells, and has a significant anti-tumor effect, reducing tumor size by up to 90% in preclinical in vivo models.

The EMA granted the clinical trial authorization for PALT1 in April 2024 and the orphan drug designation (ODD) in June 2024, confirming its interest in this innovative treatment for a serious disease. ODD provides XENOTHERA with benefits at every stage of development, including assistance with the development process, tax credit, technical assistance in preparing the application, streamlined administrative procedures, intellectual property protection and a marketing exclusivity clause once marketing authorization has been obtained. Orphan designation had already been obtained from the FDA in 2023.

The first centers to take part in the trial are the university hospitals of Caen (Professor Damaj), Clermont-Ferrand (Professor Tournilhac), Bordeaux (Professor Bouabdallah), AP-HP (Hôpital Henri-Mondor, Professor Lemonnier) and the Hospices Civils de Lyon (Hôpital Lyon-Sud, Professor Bachy). The first patient was recruited at Caen University Hospital by Professor Damaj’s teams.

PALT1 is a non-randomized, open-label phase I/II trial conducted in two stages in volunteer patients: a dose escalation phase to assess safety and tolerability and identify the maximum tolerated dose (MTD), followed by an expansion phase to assess the efficacy of PTCL treatment in relapsed/refractory patients.

"The start of this trial strengthens our position in oncology. We currently have another antibody in the clinic in solid tumors, in the FIPO trial. By entering the field of onco-hematology with the PALT1 trial, we maintain our focus on patients for whom medicine currently has no solution. I would like to thank this first patient and Professor Damaj’s teams for their confidence, and I sincerely hope that the expected benefits will be confirmed. PALT1 also supports the quality of the work done by XENOTHERA’s scientific and medical teams. Moreover, the agencies – EMA in 2024 and FDA in 2023 – are supporting our approach to patients’ needs, and reinforcing our credibility", comments Odile Duvaux, Chairman and co-founder of XENOTHERA.

On October 10, 2024 Theratechnologies Inc. ("Theratechnologies" or the "Company") (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported business highlights and financial results for the third quarter of fiscal year 2024 ended August 31, 2024 (Q3 2024). All figures are in US dollars unless otherwise stated (Press release, Theratechnologies, OCT 10, 2024, View Source [SID1234647144]).

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Revenue for the three- and nine-month periods ended August 31, 2024
(in thousands of dollars)

Three months
ended August 31 %
change Nine months
ended August 31 % change
2024 2023 2024 2023
EGRIFTA SV net sales 16,687 13,183 26.6 % 42,473 36,747 15.6 %
Trogarzo net sales 5,913 7,672 (22.9 %) 18,391 21,565 (14.7 %)
Revenue 22,600 20,855 8.4 % 60,864 58,312 4.4 %

"I am pleased to wrap up this third quarter with a strong Adjusted EBITDA of $7.2 million and a net profit of $3.1 million," said Paul Lévesque, President and Chief Executive Officer at Theratechnologies. "Quarter after quarter, we have continued to demonstrate strength on the bottom line and as such are increasing Adjusted EBITDA guidance to $17 to $19 million dollars. EGRIFTA SV remains our engine of growth, recording its best performance in recent history by capturing new patients and prescribers at an unprecedented level over the past nine months. Considering current trends for Trogarzo, and as a result of the potential constrained supply of EGRIFTA SV anticipated in late November, we are changing topline guidance to between $83 and $85 million. We believe that in the first part of 2025 we will fully make up for sales not recorded in the fourth quarter of 2024 and remain confident that any impact on patients will be avoided.

"We have doubled down on our efforts to enter into partnerships and to find innovative products to market, making significant progress in both in the U.S. and in Canada. Our North American focused strategy is clear, and we are well-positioned to achieve our long-term objective of delivering sustained top-line and bottom-line growth. In terms of our pipeline, we remain committed to bringing the F8 formulation to market and have now addressed all questions from the FDA on the sBLA related to immunogenicity and microbiology. We expect to have the file completed shortly with a plan to submit it to the FDA by the end of November. In oncology, we continue to be focused on generating results from Part 3 of our Phase 1 clinical trial of sudocetaxel zendusortide in advanced ovarian cancer and have had no reports of DLTs, including neuropathy and eye toxicities. One final patient remains in the trial and we plan to share results once their treatment is completed and all data can be analyzed."

Recent Events:

Company Announced a Risk of a Temporary Supply Disruption for EGRIFTA SV in Early 2025

On September 17, 2024, the Company announced a risk of a temporary supply disruption for EGRIFTA SV in early 2025 caused by an unexpected voluntary shutdown of the Company’s contract manufacturer’s facility following an inspection by the FDA, as well as the FDA review timeline to resume distribution of the product. The Company has since implemented measures to carefully manage the inventory levels of EGRIFTA SV to meet patient demand until mid-January 2025 and these measures will result in a revenue shortfall for EGRIFTA SV in fiscal year 2024. See "Revised Fiscal 2024 Revenue and Adjusted EBITDA Guidance" below. The manufacturer is finalizing its remediation measures and has confirmed to the Company that it plans to resume activities by mid-October. Based on these timelines, a batch of EGRIFTA SV is currently scheduled to be manufactured in the week of October 21, 2024.

Revised Fiscal 2024 Revenue and Increased Adjusted EBITDA Guidance

Theratechnologies anticipated Fiscal 2024 revenue guidance range is revised to between $83 and $85 million from $87 to $90 million. The Company hereby also increases Adjusted EBITDA guidance, a non-IFRS measure, to be between $17 and $19 million from $13 to $15 million for Fiscal 2024. This increase is supported by the Company’s continued focus on controlling expenses, as evidenced by the strong performance of the first three quarters of 2024. The revised revenue guidance takes into consideration the revenue shortfall due to the potential supply constraint of EGRIFTA SV in late November and the year-to-date trend of Trogarzo sales.

Third Quarter Fiscal 2024 Financial Results

The financial results presented in this press release are taken from the Company’s Management’s Discussion and Analysis ("MD&A") and interim consolidated financial statements ("Interim Financial Statements") for the three- and nine-month periods ended August 31, 2024 ("Third Quarter Fiscal 2024") which have been prepared in accordance with International Accounting Standard ("IAS") 34, Interim Financial Reporting of International Financial Reporting Standards ("IFRS") as issued by the International Accounting Standards Board ("IASB"). The MD&A and the Interim Financial Statements can be found on SEDAR+ at www.sedarplus.ca, on EDGAR at www.sec.gov and at www.theratech.com. Unless specified otherwise, all capitalized terms used have the meaning ascribed thereto in the Company’s MD&A.

Revenue

For the three- and nine-month periods ended August 31, 2024, consolidated revenue was $22,600,000 and $60,864,000, compared to $20,855,000 and $58,312,000 for the same periods ended August 31, 2023, representing a year-over-year increase of 8.4% for the third quarter and an increase of 4.2% for the first nine months of the fiscal year.

For the third quarter of Fiscal 2024, net sales of EGRIFTA SV were $16,687,000 compared to $13,183,000 in the third quarter of fiscal 2023, representing an increase of 26.6% year-over-year. Stronger sales of EGRIFTA SV in the third quarter of 2024 compared to the same period last year were mostly the result of strong unit demand for the product, combined with a higher net selling price than last year. Net sales for the nine-month period ended August 31, 2024 amounted to $42,473,000 compared to $36,747,000 in the same period in 2023, representing growth of 15.6%.

Trogarzo net sales in the third quarter of Fiscal 2024 amounted to $5,913,000 compared to $7,672,000 for the same quarter of 2023, representing a decrease of 22.9% year-over-year. Lower sales of Trogarzo were mostly the result of lower unit sales due to competitive pressures in the multidrug-resistant segment of the HIV-1 market, where Trogarzo remains an important part of the treatment arsenal but has lost market share to market leaders in the segment.

For the nine-month period ended August 31, 2024, Trogarzo net sales were $18,391,000 compared to $21,565,000 in the same period in 2023.

Cost of Sales

For the three- and nine-month periods ended August 31, 2024, cost of sales was $4,521,000 and $14,352,000 compared to $4,967,000 and $14,569,000 for the same periods in fiscal 2023.

Cost of Sales

Three months
ended August 31 Nine months
ended August 31
2024 2023 2024 2023
($000s) % of Revenue ($000s) % of Revenue ($000s) % of Revenue ($000s) % of Revenue
EGRIFTA SV 1,465 8.8 % 1,059 8.0 % 4,901 11.5 % 3,285 8.9 %
Trogarzo 3,056 51.7 % 3,908 50.9 % 9,451 51.4 % 11,284 52.3 %
Total 4,521 20.0 % 4,967 23.8 % 14,352 23.6 % 14,569 25.0 %

For the nine-month period ended August 31, 2024, EGRIFTA SV cost of sales was negatively affected by a $1,088,000 inventory provision ($170,000 in the comparable period of 2023) related to the manufacturing of a batch of F8 Formulation of tesamorelin, as the F8 Formulation has not yet been approved by the FDA for commercialization. No such provision was taken in the three-month period ended August 31, 2024. Trogarzo cost of sales is contractually established at 52% of net sales, subject to periodic adjustment for returns or other factors.

R&D Expenses

R&D expenses in the three- and nine-month periods ended August 31, 2024, amounted to $2,612,000 and $11,089,000 compared to $5,396,000 and $25,141,000 in the comparable periods of Fiscal 2023. R&D expenses in the nine-month period ended August 31, 2024 include the accelerated depreciation ($766,000) in the second quarter of equipment used as part of the preclinical oncology research activities, following the decision to cease early-stage R&D activities. R&D expenses in the three- and nine-month periods ended August 31, 2024 were also reduced by the recognition of Canadian federal non-refundable tax credits ($650,000).

R&D expenses
(in thousands of dollars)

Three months
ended August 31 Nine months
ended August 31
2024 2023 % change 2024 2023 % change
Oncology
Laboratory research
and personnel 78 436 -82% 1,444* 1,424 1%
Pharmaceutical
product development 60 67 -10% 217 4,410 -95%
Phase 1 clinical trial 493 204 142% 1,470 1,806 -19%
Medical projects and education 187 785 -76% 691 3,167 -78%
Salaries, benefits and expenses 1,201 2,142 -44% 3,815 7,263 -47%
Regulatory activities 367 366 - 1,174 1,164 -
Trogarzo IM formulation - 115 -100% 26 965 -97%
Tesamorelin formulation development 350 80 337% 1,402 1,201 17%
F8 human factor studies 5 534 -99% 12 1,147 -99%
Pen injector - - - - 234 -100%
European activities 53 117 -55% 105 456 -77%
Travel, consultants, patents, options, others 329 350 -6% 973 1,824 -47%
Restructuring costs 185 509 -64% 521 509 2%
Tax credits (696) (309) 125% (761) (429) 77%
Total 2,612 5,396 -52% 11,089 25,141 -56%
*Including accelerated depreciation ($766,000) of equipment used in the oncology program, following the decision to cease R&D activities related to the oncology program

R&D expenses in the second quarter of 2023 were negatively impacted by a provision of $3,042,000 related to sudocetaxel zendusortide material which could expire before the Company is able to use it in its clinical program. Theratechnologies recorded no such provision in the nine-month period ended August 31, 2024.

Selling Expenses

Selling expenses decreased to $6,307,000 and $18,375,000 for the three- and nine-month periods ended August 31, 2024, compared to $6,728,000 and $20,021,000 for the same periods last year. The decrease in selling expenses in the three- and nine-month periods ended August 31, 2024, is due in large part to tighter expense control in commercialization activities. Spending in the third quarter of Fiscal 2024 has stabilized following the completion of cost-cutting measures implemented in Fiscal 2023.

The amortization of the intangible asset value for the EGRIFTA SV and Trogarzo commercialization rights is also included in selling expenses. As such, the Company recorded amortization expense of $360,000 and $1,080,000 for the three- and nine-month periods ended August 31, 2024 compared to $675,000 and $2,153,000 in the same periods of Fiscal 2023.

General and Administrative Expenses

General and administrative expenses in the three- and nine-month periods ended August 31, 2024, amounted to $2,947,000 and $9,793,000 compared to $3,710,000 and $11,878,000 reported in the comparable periods of Fiscal 2023. The decrease in General and Administrative expenses is largely due to the implementation of cost-cutting measures announced in Fiscal 2023.

Adjusted EBITDA

Adjusted EBITDA was $7,239,000 for the third quarter of fiscal 2024 and $12,451,000 for the nine-month period ended August 31, 2024, compared to $2,160,000 and $(7,872,000) for the same periods of Fiscal 2023. See "Non-IFRS and Non-US-GAAP Measure" below and see "Reconciliation of Adjusted EBITDA" below for a reconciliation to Net Loss for the relevant periods.

Net Finance Costs

Net finance costs for the three- and nine-month periods ended August 31, 2024, were $2,366,000 and $6,674,000 compared to $674,000 and $7,557,000 for the comparable periods of Fiscal 2023. Net finance costs in the third quarter of Fiscal 2024 included interest of $2,295,000, versus $2,244,000 in the third quarter of Fiscal 2023. Net finance costs in the nine-month period ended August 31, 2024 included interest of $6,882,000 versus $5,902,000 in the nine-month period of Fiscal 2023. During the nine-month period ended on August 31, 2023, net finance costs were also impacted by the loss on Loan Facility modification of $2,650,000 related to the issuance of common share purchase warrants (the "Marathon Warrants") issued in connection with the amendments to the credit agreement entered into with affiliates of Marathon Asset Management (the "Credit Agreement").

Net finance costs for the three- and nine-month periods ended August 31, 2024, also included accretion expense of $366,000 and $1,122,000, compared to $500,000 and $1,642,000 for the comparable periods in 2023.

Income Taxes

During the three- and nine-month periods ended August 31, 2024, income tax expenses amounted to $756,000 and $984,000, versus $126,000 and $348,000 in the same period last year. The increase in the third quarter of 2024 over previous quarters is related to the higher net income generated by our operations. The Company recorded Canadian federal non-refundable tax credits in the three-month period ended August 31, 2024 ($650,000) against research and development expenses, which largely offsets the higher income tax expense.

Net Income (Loss)

As a result of stronger revenues and the tight management of expenses over the past year, net income for the third quarter ended August 31, 2024, amounted to $3,091,000 compared to a net loss of $746,000 in 2023. For the nine-month periods ended August 31, 2024 and 2023 the Company recorded net losses of $403,000 and $21,202,000, respectively.

Financial Position, Liquidity and Capital Resources

Liquidity and Going Concern

As part of the preparation of the Interim Consolidated Financial Statements, management is responsible for identifying events or conditions that indicate a material uncertainty exists that casts substantial doubt on the Company’s ability to continue to honor its obligations as they fall due during a period of at least, but not limited to, 12 months from August 31, 2024. If the Company concludes that events or conditions indicate material uncertainty exists on its ability to continue as a going concern, it must assess whether management’s plans developed to mitigate these events or conditions address the material uncertainty.

For the nine-month period ended August 31, 2024, the Company generated a net loss of $403,000 (2023-net loss of $21,202,000) and had cash flows from operating activities of $2,606,000 (2023- negative $1,572,000). As at August 31, 2024, cash amounted to $34,690,000 and bonds and money market funds amounted to $4,169,000.

The Company’s Marathon Credit Agreement (as defined in Note 7 of the Interim Financial Statements) contains various covenants, including minimum liquidity covenants whereby the Company needs to maintain significant cash, cash equivalent and eligible short-term investments balances in specified accounts, which restricts the management of the Company’s liquidity (refer to Note 7 of the Interim Financial Statements). As at August 31, 2024, the material covenants of the Marathon Credit Agreement include: (i) minimum liquidity of $17,500,000; and (ii) minimum Marathon Adjusted EBITDA targets over the most recently ended four fiscal quarters. A breach of a covenant provides the lender with the ability to demand immediate repayment of the Loan Facility (as defined in Note 7 of the Interim Financial Statements) and makes available to the lender the collateralized assets, which include substantially all cash, bonds and money market funds which are subject to control agreements. Although the lender has previously waived or amended the agreement for breaches of covenants, there is no assurance that the lender will agree to waive or amend future covenant breaches, if any. The Company does not currently have other committed sources of financing available to it.

On September 17, 2024, the Company announced a risk of a temporary supply disruption for EGRIFTA SV in early 2025 caused by an unexpected voluntary shutdown of the Company’s contract manufacturer’s facility following an inspection by the FDA, as well as the FDA review timeline to resume distribution of the product. The manufacturer is finalizing its remediation measures and has confirmed to the Company that it plans to resume activities by mid-October. Based on these timelines, a batch of EGRIFTA SV is currently scheduled to be manufactured in the week of October 21, 2024. In order to resume distribution of EGRIFTA SV, the Company was requested by the FDA to file a Prior Approval Supplement ("PAS") describing the changes made by its manufacturer. The Company plans to file the PAS in early November 2024. A PAS is usually reviewed by the FDA within four months of receipt.

The Company’s ability to continue generating revenues through the sale of EGRIFTA SV and to be able to meet the Marathon Adjusted EBITDA targets for a period of at least, but not limited to, 12 months from August 31, 2024, involves significant judgement and is dependent on the resumption of the manufacture and distribution of EGRIFTA SV by the end of the first quarter of fiscal 2025, which is dependant on the release to the market of the new batch of EGRIFTA SV. This also involves management of expenses to remain in compliance with the conditions of the Marathon Credit Agreement. The Company would need to obtain the support of the lender (including possible waivers and amendments, if necessary) in the event of a breach of the covenants in the Marathon Credit Agreement. Should management’s plans not materialize, the Company may be in default under the Marathon Credit Agreement, be forced to reduce or delay expenditures and capital additions and seek additional alternative financing, or sell or liquidate its assets. Portions of management’s plans are outside of their control such as the timing of resumption of product distribution which requires FDA approval. Therefore, there are scenarios wherein events or conditions combine to create material uncertainty and cast substantial doubt about the Company’s ability to continue as a going concern.

The Interim Consolidated Financial Statements have been prepared assuming the Company will continue as a going concern, which assumes the Company will continue its operations in the foreseeable future and will be able to realize its assets and discharge its liabilities and commitments in the normal course of business. The Interim Consolidated Financial Statements do not include any adjustments to the carrying values and classification of assets and liabilities and reported expenses that might result from the outcome of this uncertainty and that may be necessary if the going concern basis was not appropriate for the Interim Consolidated Financial Statements. If the Company was unable to continue as a going concern, material impairment of the carrying values of the Company’s assets, including intangible assets, could be required.

Analysis of cash flows

Theratechnologies ended the third quarter of Fiscal 2024 with $34,690,000 in cash, and $4,169,000 in bonds and money market funds. Available cash is invested in highly liquid fixed income instruments including governmental and municipal bonds, and money market funds.

For the three-month period ended August 31, 2024, cash flow from operating activities before changes in operating assets and liabilities improved to $4,060,000, compared to a cash usage of $1,270,000 in the comparable period of Fiscal 2023, or an improvement of $5,330,000.

In the third quarter of Fiscal 2024, changes in operating assets and liabilities had a positive impact on cash flow of $544,000 (2023-positive impact of $6,599,000). These changes included positive impacts from lower accounts receivable ($2,539,000) and from a decrease in prepaid expenses and deposits ($511,000), and also include a negative impact from lower accounts payable ($2,329,000) and higher inventories ($455,000).

During the third quarter of Fiscal 2024, cash flows from financing activities used $1,868,000 in cash, mostly related to the payment of the first of 36 monthly payments ($1,683,000) related to the amortization of the Marathon loan, while investing activities generated $779,000 from the sale bonds and money market funds. During the nine-month period ended August 31, 2024, investing activities also include cash used for the payment of the second milestone to TaiMed Biologics related to the approval of the IV push method of administration of Trogarzo ($1,500,000).

Non-IFRS and Non-U.S. GAAP Measure

The information presented in this press release includes a measure that is not determined in accordance with IFRS or U.S. generally accepted accounting principles ("U.S. GAAP"), being the term "Adjusted EBITDA". "Adjusted EBITDA" is used by the Company as an indicator of financial performance and is obtained by adding to net profit or loss, finance income and costs, depreciation and amortization, income taxes, share-based compensation from stock options, and certain write-downs (or related reversals) of inventories. "Adjusted EBITDA" excludes the effects of items that primarily reflect the impact of long-term investment and financing decisions rather than the results of day-to-day operations. The Company believes that this measure can be a useful indicator of its operational performance from one period to another. The Company uses this non-IFRS measure to make financial, strategic and operating decisions. Adjusted EBITDA is not a standardized financial measure under the financial reporting framework used to prepare the financial statements of the Corporation to which the measure relates and might not be comparable to similar financial measures disclosed by other issuers. A quantitative reconciliation of the Adjusted EBITDA is presented in the table below:

Reconciliation of Adjusted EBITDA
(In thousands of dollars)

Three-month periods ended
August 31
Nine-month periods ended
August 31

2024 2023 2024 2023
Net income (loss) 3,091 (746 ) (403 ) (21,202 )
Add :
Depreciation and amortization2 489 868 2,268 2,739
Net Finance costs3 2,366 674 6,674 7,557
Income tax expense 756 126 984 348
Share-based compensation 387 519 1,354 1,797
Inventory provision4 - - 1,088 170
Restructuring costs 150 719 486 719
Adjusted EBITDA 7,239 2,160 12,451 (7,872 )

Conference Call Details

The call will be held on Thursday, October 10 at 8:30 a.m. ET and will be hosted by Paul Lévesque, President and Chief Executive Officer. He will be joined by other members of the management team, including Philippe Dubuc, Senior Vice President and Chief Financial Officer, Christian Marsolais, Ph.D., Senior Vice President and Chief Medical Officer and John Leasure, Global Commercial Officer who will be available to answer questions from participants following prepared remarks.

Participants are encouraged to join the call at least ten minutes in advance to secure access. Conference call dial-in and replay information can be found below.

On October 10, 2024 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-classi targeted and immune-mediated therapeutics to fight cancer, reported an agreement with Roche to advance the evaluation of amezalpat (TPST-1120) in combination with atezolizumab (Tecentriq) and bevacizumab, the current standard of care for unresectable or metastatic hepatocellular carcinoma (HCC), into a pivotal Phase 3 trial for the first-line treatment of unresectable or metastatic hepatocellular carcinoma, a form of liver cancer with high unmet need (Press release, Tempest Therapeutics, OCT 10, 2024, View Source [SID1234647143]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Under the agreement, Roche will supply atezolizumab globally and Tempest will sponsor and lead the pivotal study. This agreement builds on a clinical collaboration between the companies pursuant to which amezalpat was combined with atezolizumab and bevacizumab in first-line HCC patients and compared to atezolizumab and bevacizumab alone in a randomized Phase 1b/2 study. Tempest retains all development and commercial rights to amezalpat.

"We’re excited to announce this agreement that supports the advancement of amezalpat into a pivotal study and reinforces both Tempest and Roche’s shared commitment to delivering groundbreaking cancer treatments for patients," said Stephen Brady, president and chief executive officer of Tempest. "Based on the positive Phase 2 data, I believe this combination therapy holds the potential to significantly improve first-line liver cancer treatment, and we look forward to amezalpat moving into this pivotal Phase 3 study."

In June, Tempest reported updated positive survival data from the ongoing global randomized Phase 1b/2 clinical study, demonstrating a six-month improvement in median overall survival (OS) for patients receiving the combination therapy, in comparison to the control arm of atezolizumab and bevacizumab alone in the first-line treatment of patients with unresectable or metastatic HCC. The survival benefit observed in the amezalpat arm was maintained in key subpopulations, as well. These June data build upon previously released data from the primary analysis showing that the amezalpat combination therapy provided clinical benefit regardless of PD-L1 status and in patients with both immune excluded and immune desert tumors. Patients with a mutation in the beta catenin gene had an increased objective response rate and, in the updated data set, a longer median OS, both supported by amezalpat’s purported mechanism of action.

In August, the company held its end-of-phase 2 meeting with the FDA where it reached broad agreement on the Phase 3 study plan, including the amezalpat dose schedule and primary endpoint of OS, which was a positive result from the Phase 2. The FDA also agreed on the statistical plan, including a pre-specified early efficacy analysis that the company currently estimates could shorten the study’s timeline to primary analysis by 8 months.

About the TPST-1120-301 Study

The planned Phase 3 study is a global, blinded, 1:1 randomized study of amezalpat plus atezolizumab and bevacizumab vs. atezolizumab and bevacizumab, the standard of care, in patients with unresectable or metastatic HCC treated in the first line setting. In August 2024, the company received agreement from the FDA on its Phase 3 study design, dose of amezalpat, and the statistical plan, including a pre-specified efficacy analysis that could shorten the time to primary analysis. The company is preparing for the Phase 3 study start in the first quarter of 2025.

About Amezalpat (TPST-1120)

Amezalpat is an oral, small molecule, selective PPAR⍺ antagonist. Data suggest that amezalpat treats cancer by targeting tumor cells directly and by modulating immune suppressive cells and angiogenesis in the tumor microenvironment. In an ongoing global randomized phase 1b/2 study of amezalpat in combination with atezolizumab and bevacizumab in first-line patients with advanced HCC, the amezalpat arm showed clinical superiority across multiple study endpoints, including overall survival in both the overall population and key subpopulations, when compared to atezolizumab and bevacizumab alone, the standard of care. These randomized data were supported by positive results observed in the Phase 1 clinical trial in patients with heavily pretreated advanced solid tumors, including renal cell carcinoma and cholangiocarcinoma.

On October 10, 2024 Pfizer Inc. (NYSE: PFE) reported positive topline results from the final prespecified overall survival (OS) analysis of the TALAPRO-2 study of TALZENNA (talazoparib), an oral poly ADP-ribose polymerase (PARP) inhibitor, in combination with XTANDI (enzalutamide), an androgen receptor pathway inhibitor (ARPI), in patients with metastatic castration-resistant prostate cancer (mCRPC) (Press release, Seagen, OCT 10, 2024, View Source [SID1234647142]). Results showed a statistically significant and clinically meaningful improvement in the final OS in all-comers (cohort 1) as well as in those patients with homologous recombination repair (HRR) gene-mutated mCRPC (cohort 2), compared to XTANDI alone.

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"The TALAPRO-2 results showed that TALZENNA plus XTANDI is the first and only PARP inhibitor in combination with an ARPI to significantly improve survival in patients with metastatic castration-resistant prostate cancer, regardless of mutation status," said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. "Pfizer is dedicated to advancing scientific breakthroughs in genitourinary cancers, and these exciting TALAPRO-2 results further highlight our long-standing commitment to improving survival for men with prostate cancer."

"These overall survival results indicate potentially practice-changing efficacy for TALZENNA in combination with XTANDI for men with metastatic castration-resistant prostate cancer," said Neeraj Agarwal, M.D., FASCO, Professor and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute, University of Utah, and global lead investigator for TALAPRO-2. "Metastatic castration-resistant prostate cancer is the most advanced and aggressive stage of the disease, and the TALAPRO-2 results provide much-needed hope to patients who remain in high unmet need for effective treatment options."

At the time of the final analysis, the clinically meaningful improvement in radiographic progression free survival (rPFS) was maintained in both cohorts from the prior primary analysis previously reported and published in The Lancet . In addition, the safety profile of TALZENNA plus XTANDI was generally consistent with the known safety profile of each medicine. Detailed results from TALAPRO-2 will be submitted for presentation at an upcoming medical congress. These data will also be shared with global health authorities to potentially support regulatory filings to update and potentially expand the approved label for TALZENNA.

TALZENNA in combination with XTANDI was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with HRR gene-mutated mCRPC in June 2023. The combination was also approved by the European Commission in January 2024 for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated. TALZENNA is the first and only PARP inhibitor licensed in the European Union for use with XTANDI for patients with mCRPC, with or without gene mutations. TALZENNA in combination with XTANDI is now approved in more than 35 countries globally for patients with mCRPC.

About Metastatic Castration-Resistant Prostate Cancer

Prostate cancer is the second most common cancer in men and the fifth most common cause of cancer death among men worldwide, with an estimated 1.4 million new cases diagnosed in 2022. 1 In the U.S., it is the most common cancer in men. 2 mCRPC is a cancer that has spread beyond the prostate gland and has progressed despite medical or surgical treatment to lower testosterone. Approximately 10%–20% of prostate cancer patients develop mCRPC within 5−7 years of diagnosis. 3 Between 1.2%–2.1% of all prostate cancer cases globally are mCRPC. 4

About TALAPRO-2

The Phase 3 TALAPRO-2 trial is a multicenter, randomized, double-blind, placebo-controlled study that enrolled 1,035 unique patients with mCRPC (who had not received new life-prolonging systemic treatments after documentation of mCRPC) at sites in the U.S., Canada, Europe, South America, and the Asia-Pacific region. The study included two patient cohorts: all-comers (n=805, of whom 169 had HRR mutations and 636 did not) and those with HRR gene mutations (n=399, including 169 patients from Cohort 1 and 230 enrolled in Cohort 2). Patients with castrate testosterone levels were randomized to receive TALZENNA 0.5 mg/day plus XTANDI 160mg/day, or placebo plus XTANDI 160mg/day.

The primary endpoint of the trial was rPFS, defined as the time from the date of randomization to first objective evidence of radiographic progression by blinded independent review, or death, whichever occurred first, in both Cohort 1 (all-comers) and Cohort 2 (those with HRRm). Secondary endpoints included OS, objective response rate (ORR), duration of response (DOR), and prostate-specific antigen (PSA) response.

For more information on the TALAPRO-2 trial (NCT03395197), go to www.clinicaltrials.gov.

About TALZENNA (talazoparib)

TALZENNA is an oral inhibitor of poly ADP-ribose polymerase (PARP), which plays a role in DNA damage repair. Preclinical studies have demonstrated that TALZENNA blocks PARP enzyme activity and traps PARP at the site of DNA damage, leading to decreased cancer cell growth and cancer cell death.

TALZENNA is approved in the U.S., EU, and multiple other regions for the treatment of adult patients with deleterious or suspected deleterious gBRCAm HER2-negative locally advanced or metastatic breast cancer. In the U.S., TALZENNA is approved in combination with XTANDI for the treatment of adult patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC). In the EU, TALZENNA is approved in combination with enzalutamide for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated.

TALZENNA (talazoparib) Indication in the U.S.

TALZENNA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for:

HRR gene-mutated mCRPC:

In combination with enzalutamide for the treatment of adult patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).
Breast Cancer:

As a single agent, for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer. Select patients for therapy based on an FDA-approved companion diagnostic for TALZENNA.
TALZENNA (talazoparib) Important Safety Information

WARNINGS and PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) , including cases with a fatal outcome, has been reported in patients who received TALZENNA. Overall, MDS/AML has been reported in 0.4% (3 out of 788) of solid tumor patients treated with TALZENNA as a single agent in clinical studies. In TALAPRO-2, MDS/AML occurred in 2 out of 511 (0.4%) patients treated with TALZENNA and enzalutamide and in 0 out of 517 (0%) patients treated with placebo and enzalutamide. The durations of TALZENNA treatment in these five patients prior to developing MDS/AML were 0.3, 1, 2, 3, and 5 years, respectively. Most of these patients had received previous chemotherapy with platinum agents and/or other DNA damaging agents including radiotherapy.

Do not start TALZENNA until patients have adequately recovered from hematological toxicity caused by previous chemotherapy. Monitor blood counts monthly during treatment with TALZENNA. For prolonged hematological toxicities, interrupt TALZENNA and monitor blood counts weekly until recovery. If counts do not recover within 4 weeks, refer the patient to a hematologist for further investigations including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue TALZENNA.

Myelosuppression consisting of anemia, neutropenia, and/or thrombocytopenia have been reported in patients treated with TALZENNA. In TALAPRO-2, Grade ≥3 anemia, neutropenia, and thrombocytopenia were reported, respectively, in 45%, 18%, and 8% of patients receiving TALZENNA and enzalutamide. Overall, 39% of patients (199/511) required a red blood cell transfusion, including 22% (111/511) who required multiple transfusions. Discontinuation due to anemia, neutropenia, and thrombocytopenia occurred, respectively, in 7%, 3%, and 0.4% of patients.

Withhold TALZENNA until patients have adequately recovered from hematological toxicity caused by previous therapy. Monitor blood counts monthly during treatment with TALZENNA. If hematological toxicities do not resolve within 28 days, discontinue TALZENNA and refer the patient to a hematologist for further investigations including bone marrow analysis and blood sample for cytogenetics.

Embryo-Fetal Toxicity TALZENNA can cause fetal harm when administered to pregnant women. Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment with TALZENNA and for 4 months after receiving the last dose.

ADVERSE REACTIONS

In TALAPRO-2, serious adverse reactions reported in >2% of patients included anemia (9%) and fracture (3%). Fatal adverse reactions occurred in 1.5% of patients, including pneumonia, COVID infection, and sepsis (1 patient each).

The most common adverse reactions (≥ 10%, all Grades), including laboratory abnormalities, for patients in the TALAPRO-2 study who received TALZENNA in combination with enzalutamide vs patients receiving placebo with enzalutamide were hemoglobin decreased (79% vs 34%), neutrophils decreased (60% vs 18%), lymphocytes decreased (58% vs 36%), fatigue (49% vs 40%), platelets decreased (45% vs 8%), calcium decreased (25% vs 11%), nausea (21% vs 17%), decreased appetite (20% vs 14%), sodium decreased (22% vs 20%), phosphate decreased (17% vs 13%), fractures (14% vs 10%), magnesium decreased (14% vs 12%), dizziness (13% vs 9%), bilirubin increased (11% vs 7%), potassium decreased (11% vs 7%), and dysgeusia (10% vs 4.5%).

Clinically relevant adverse reactions in <10% of patients who received TALZENNA with enzalutamide included abdominal pain (9%), vomiting (9%), alopecia (7%), dyspepsia (4%), venous thromboembolism (3%) and stomatitis (2%).

Based on animal studies, TALZENNA may impair fertility in males of reproductive potential.

DRUG INTERACTIONS

Coadministration with P-gp inhibitors The effect of coadministration of P-gp inhibitors on talazoparib exposure when TALZENNA is taken in combination with enzalutamide has not been studied. Monitor patients for increased adverse reactions and modify the dosage as recommended for adverse reactions when TALZENNA is coadministered with a P-gp inhibitor.

Coadministration with BCRP inhibitors Monitor patients for increased adverse reactions and modify the dosage as recommended for adverse reactions when TALZENNA is coadministered with a BCRP inhibitor. Coadministration of TALZENNA with BCRP inhibitors may increase talazoparib exposure, which may increase the risk of adverse reactions.

USE IN SPECIFIC POPULATIONS

Renal Impairment The recommended dosage of TALZENNA for patients with moderate renal impairment (CLcr 30 – 59 mL/min) is 0.35 mg taken orally once daily in combination with enzalutamide. The recommended dosage of TALZENNA for patients with severe renal impairment (CLcr 15 – 29 mL/min) is 0.25 mg taken orally once daily in combination with enzalutamide. No dose adjustment is required for patients with mild renal impairment. TALZENNA has not been studied in patients requiring hemodialysis.

Please see full U.S. Prescribing Information and Patient Information for TALZENNA (talazoparib) at www.TALZENNA.com.

About XTANDI (enzalutamide) and Important Safety Information

XTANDI (enzalutamide) is an androgen receptor signaling inhibitor. XTANDI is a standard of care and has received regulatory approvals in one or more countries around the world for use in men with metastatic castration-sensitive prostate cancer (mCSPC; also known as metastatic hormone-sensitive prostate cancer or mHSPC), metastatic castration-resistant prostate cancer (mCRPC), non-metastatic castration-resistant prostate cancer (nmCRPC) and nonmetastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR). XTANDI is currently approved for one or more of these indications in more than 90 countries, including in the U.S., EU, and Japan. Over one million patients have been treated with XTANDI globally. 5

Warnings and Precautions

Seizure occurred in 0.6% of patients receiving XTANDI in eight randomized clinical trials. In a study of patients with predisposing factors for seizure, 2.2% of XTANDI-treated patients experienced a seizure. It is unknown whether anti-epileptic medications will prevent seizures with XTANDI. Patients in the study had one or more of the following predisposing factors: use of medications that may lower the seizure threshold, history of traumatic brain or head injury, history of cerebrovascular accident or transient ischemic attack, and Alzheimer’s disease, meningioma, or leptomeningeal disease from prostate cancer, unexplained loss of consciousness within the last 12 months, history of seizure, presence of a space occupying lesion of the brain, history of arteriovenous malformation, or history of brain infection. Advise patients of the risk of developing a seizure while taking XTANDI and of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) There have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder that can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Hypersensitivity reactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with XTANDI in eight randomized clinical trials. Pharyngeal edema has been reported in post-marketing cases. Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Permanently discontinue XTANDI for serious hypersensitivity reactions.

Ischemic Heart Disease In the combined data of five randomized, placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (3.5% vs 2%). Grade 3-4 ischemic events occurred in 1.8% of patients on XTANDI versus 1.1% on placebo. Ischemic events led to death in 0.4% of patients on XTANDI compared to 0.1% on placebo. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue XTANDI for Grade 3-4 ischemic heart disease.

Falls and Fractures occurred in patients receiving XTANDI. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents. In the combined data of five randomized, placebo-controlled clinical studies, falls occurred in 12% of patients treated with XTANDI compared to 6% of patients treated with placebo. Fractures occurred in 13% of patients treated with XTANDI and in 6% of patients treated with placebo.

Embryo-Fetal Toxicity The safety and efficacy of XTANDI have not been established in females. XTANDI can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment with XTANDI and for 3 months after the last dose of XTANDI.

Adverse Reactions (ARs) the data from the five randomized placebo-controlled trials, the most common ARs (≥ 10%) that occurred more frequently (≥ 2% over placebo) in XTANDI-treated patients were musculoskeletal pain, fatigue, hot flush, constipation, decreased appetite, diarrhea, hypertension, hemorrhage, fall, fracture, and headache. In the bicalutamide-controlled study, the most common ARs (≥ 10%) reported in XTANDI-treated patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, diarrhea, upper respiratory tract infection, and weight loss.

In AFFIRM, the placebo-controlled study of metastatic CRPC (mCRPC) patients who previously received docetaxel, Grade 3 and higher ARs were reported among 47% of XTANDI-treated patients. Discontinuations due to ARs were reported for 16% of XTANDI-treated patients. In PREVAIL, the placebo-controlled study of chemotherapy-naive mCRPC patients, Grade 3-4 ARs were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to ARs were reported for 6% of XTANDI-treated patients. In TERRAIN, the bicalutamide-controlled study of chemotherapy-naive mCRPC patients, Grade 3-4 ARs were reported in 39% of XTANDI patients and 38% of bicalutamide patients. Discontinuations with an AR as the primary reason were reported for 8% of XTANDI patients and 6% of bicalutamide patients.

In PROSPER, the placebo-controlled study of nonmetastatic CRPC (nmCRPC) patients, Grade 3 or higher ARs were reported in 31% of XTANDI patients and 23% of placebo patients. Discontinuations with an AR as the primary reason were reported for 9% of XTANDI patients and 6% of placebo patients.

In ARCHES, the placebo-controlled study of metastatic CSPC (mCSPC) patients, Grade 3 or higher ARs were reported in 24% of XTANDI-treated patients. Permanent discontinuation due to ARs as the primary reason was reported in 5% of XTANDI patients and 4% of placebo patients.

In EMBARK, the placebo-controlled study of nonmetastatic CSPC (nmCSPC) with high-risk biochemical recurrence (BCR) patients, Grade 3 or higher adverse reactions during the total duration of treatment were reported in 46% of patients treated with XTANDI plus leuprolide, 50% of patients receiving XTANDI as a single agent, and 43% of patients receiving placebo plus leuprolide. Permanent treatment discontinuation due to adverse reactions during the total duration of treatment as the primary reason was reported in 21% of patients treated with XTANDI plus leuprolide, 18% of patients receiving XTANDI as a single agent, and 10% of patients receiving placebo plus leuprolide.

Lab Abnormalities : Lab abnormalities that occurred in ≥ 5% of patients, and more frequently (> 2%) in the XTANDI arm compared to placebo in the pooled, randomized, placebo-controlled studies are hemoglobin decrease, neutrophil count decreased, white blood cell decreased, hyperglycemia, hypermagnesemia, hyponatremia, hyperphosphatemia, and hypercalcemia.

Hypertension: In the combined data from five randomized placebo-controlled clinical trials, hypertension was reported in 14.2% of XTANDI patients and 7.4% of placebo patients. Hypertension led to study discontinuation in < 1% of patients in each arm.

Drug Interactions

Effect of Other Drugs on XTANDI Avoid coadministration with strong CYP2C8 inhibitors. If coadministration cannot be avoided, reduce the dosage of XTANDI.

Avoid coadministration with strong CYP3A4 inducers. If coadministration cannot be avoided, increase the dosage of XTANDI.

Effect of XTANDI on Other Drugs Avoid coadministration with certain CYP3A4, CYP2C9, and CYP2C19 substrates for which minimal decrease in concentration may lead to therapeutic failure of the substrate. If coadministration cannot be avoided, increase the dosage of these substrates in accordance with their Prescribing Information. In cases where active metabolites are formed, there may be increased exposure to the active metabolites.