Threitolceramide 6 (Portage Biotech)

Updated data support the proof of concept of using an iNKT engager monotherapy (PORT-2) to induce immune response for patients with non-small cell lung cancer (NSCLC) and melanoma Strong academic interest in the design of the Adenosine 2A(A2A) and Adenosine 2B(A2B) trial for patients with solid tumors with high adenosine receptor expression WESTPORT, Conn., Nov. 06, 2023 (GLOBE NEWSWIRE) --Portage Biotech Inc. (NASDAQ: PRTG), a clinical-stage immuno-oncology company developing therapies to improve patient lives and increase survival, today announced the presentations of updates from its ongoing IMPORT-201 Phase 1/2 trial of PORT-2 (IMM60), an invariant natural killer T cell (iNKT) engager for patients with NSCLC and advanced melanoma, and its ADPORT-601 adaptive Phase 1a/1b trial for PORT-6 (A2A inhibitor) and PORT-7 (A2B inhibitor) in multiple solid tumors at SITC. The patient data from IMPORT-201, a multi-arm Phase 1/2 trial evaluating PORT-2 in multiple settings, included front-line and refractory NSCLC, and refractory melanoma, as a monotherapy and in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab). These data build on previous results shared at the 2023 American Society of Clinical Oncology (ASCO) meeting in June and include new information on the novel pharmacology pro PORT-2. “We are encouraged by the expanding patient data set that supports results showing PORT-2 having a favorable safety and tolerability pro a monotherapy as well as early combination data,” said Dr. Ian Walters, Chief Executive Officer of Portage Biotech. “We continue to see single agent activity of PORT-2 at the 3 and 9 mg/m2 dose. We are looking forward to exploring higher dose levels as monotherapy and in combination." Dr. Sumit K. Subudhi from the University of Texas MD Anderson Cancer Center presented the design of the ADPORT-601 trial. This trial will evaluate a potent and selective A2A inhibitor (PORT-6), and an A2B inhibitor (PORT-7), alone and in combination with other immunotherapies specifically in tumors that overexpress adenosine. This trial is being conducted in collaboration with Merck and is being designed to explore A2A + pembrolizumab, A2B + pembrolizumab, and the triplet of A2A + A2B (both at the optimal biologic dose) + pembrolizumab. Dr. Subudhi commented, “Portage’s potentially best-in-class A2A and A2B compounds coupled with a keen focus on patient selection and translational endpoints make this trial very appealing. I especially appreciate Portage’s proactive approach to understanding the immune effects of modulating the adenosine pathway early in their development program.” SITC presentations are available now to registrants through the conference platform. Both posters will be added to the “Presentations & Publications” section of Portage’s website following the conference. Presentation Details: Abstract Title: ADPORT-601 (TT-10-101): First-in-Human Study of Adenosine 2A (A2A) and Adenosine 2B (A2B) receptor antagonists in Participants with Selected Advanced Solid Tumors Presenter/First Author: Sumit K. Subudhi, University of Texas MD Anderson Cancer Center Abstract Number: 759 Abstract Title: IMP-MEL: A phase 1 first-in-human dose-finding study of a novel invariant natural killer T-cell agonist (iNKT) IMM60 in advanced melanoma and non-small-cell lung cancer (NSCLC) Presenter/First Author: Nicholas Coupe, MBBS, Oxford University Hospital, Oxford, United Kingdom Abstract Number: 712 About IMPORT-201 The IMPORT-201 trial is a multicenter multi-arm Phase 1/2 trial evaluating PORT-2 (IMM60) in metastatic non-small cell lung cancer and advanced melanoma. The Phase 1 portion of the trial seeks to establish the recommended Phase 2 dose of PORT-2 alone or in combination with pembrolizumab. To learn more about the study, visit clinicaltrials.gov. About ADPORT-601 The ADPORT-601 adaptive Phase 1a/1b study will explore Portage Biotech’s small molecule adenosine antagonists, PORT-6 and PORT-7, as monotherapies, in combination with one another and potentially in combination with other Portage assets. Phase 1a will evaluate the safety of PORT-6 and PORT-7 both as a monotherapy and in combination with immune checkpoint inhibitors, with the goal of identifying a recommended Phase 2 dose. Phase 1b is designed to explore PORT-6 and PORT-7 monotherapies in an enriched population and in randomized trials versus standard of care. To learn more about the study, visit clinicaltrials.gov. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About Portage Biotech Inc. Portage is a clinical-stage immuno-oncology company advancing multi-targeted therapies to extend survival and significantly improve the lives of patients with cancer. Lead programs in the Portage portfolio include first-in-class invariant natural killer T cell (iNKT) small molecule engagers and potentially best-in-class adenosine antagonists. These programs are being advanced using innovative trial designs and translational data to identify the patient populations most likely to benefit from treatment. The Company’s unique business model leverages a strong network of academic experts and large pharma partners to rapidly and efficiently advance multiple products. For more information, please visit follow us on Twitter at @PortageBiotech or find us on LinkedIn at Portage Biotech Inc. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Statements in this press release that are not statements of historical fact are forward-looking statements. Words such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “estimate,” “believe,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions are intended to identify forward-looking statements, though not all forward-looking statements contain these identifying words. Forward-looking statements in this press release include statements concerning, among other things, the Company's belief that targeting the adenosine pathway could improve outcomes in multiple cancer types; the Company's belief that PORT-6 is more potent, durable and selective than other agents; the Company's commitment to advancing the PORT-6 program along with its ongoing development of its iNKT agonist; the Company's plan to evaluate PORT-7 as part of the ADPORT Phase 1a/1b trial; the Company's expectation that PORT-7 will allow for customization of treatment for any given tumor type to identify patients that are likely to respond and have potential to benefit most from treatment; the expectation that the PORT-6 A2AR inhibitor and PORT-7 A2BR inhibitor trial will provide insight into understanding of the therapeutic implications of targeting each pathway alone or in combination at optimum biologic doses in multiple cancer types; the ability of the Company’s clinical trials to provide insights into potentially improving patient selection strategies by selecting patients whose tumors have a high level of adenosine expression; and the expected benefits of adenosine and its potential impact on the future of cancer treatment. As a result, forward-looking statements are subject to certain risks and uncertainties, including, but not limited to: the Company’s plans and ability to develop and commercialize its product candidates and the timing of its development programs; the Company’s clinical development of its product candidates, including the results of current and future clinical trials; the benefits and risks of the Company’s product candidates as compared to others; the Company’s maintenance and establishment of intellectual property rights in its product candidates; the Company’s need for financing and its estimates regarding its capital requirements and future revenues and profitability; the Company’s estimates of the size of the potential markets for its product candidates; its selection and licensing of product candidates; and other factors set forth in “Item 3 - Key Information - Risk Factors” in the Company’s Annual Report on Form 20-F for the year ended March 31, 2023. Although the Company believes that the expectations reflected in these forward-looking statements are reasonable, undue reliance should not be placed on them as actual results may differ materially from these forward-looking statements. The forward-looking statements contained in this press release are made as of the date hereof, and the Company undertakes no obligation to update publicly or revise any forward-looking statements or information, except as required by law. FOR MORE INFORMATION, PLEASE CONTACT: Investor Relations: ir@portagebiotech.com Media Relations: media@portagebiotech.com

Company poised to accelerate accrual in all clinical programs as it activates numerous sites across multiple U.S. cities and abroad and takes over sponsorship from the investigator-led programUpdated interim data for lead iNKT engager, PORT-2, presented at the 2023 ASCO Annual Meeting showed early evidence of monotherapy activity with minimal toxicityFirst patient dosed in Phase 1a trial of PORT-6 (A2AR antagonist) in select solid tumors WESTPORT, Conn., July 31, 2023 (GLOBE NEWSWIRE) -- Portage Biotech Inc. (NASDAQ: PRTG), a clinical-stage immuno-oncology company advancing novel multi-targeted therapies for use as monotherapy and in combination, today announced financial results for the fiscal year ended March 31, 2023. “We continue to advance our clinical programs with important progress made recently in both our iNKT engager and adenosine programs and are pleased to see the trials generating interest from the academic community,” said Dr. Ian Walters, Chief Executive Officer and Chairman of Portage Biotech. “At ASCO we presented favorable interim data from the Phase 1/2 trial of our lead program, PORT-2 for the treatment of patients with advanced melanoma and metastatic non-small cell lung cancer. The presented data showed early evidence of monotherapy activity and meaningful reduction of several target lesions with minimal toxicity. This has led to our expansion of the trial globally and transition of sponsorship from the academic sponsor to Portage.” “We also recently announced the dosing of the first patient in our adaptive Phase 1a/1b trial, ADPORT-601 (NCT04969315), evaluating PORT-6, our adenosine 2A receptor (A2AR) antagonist candidate, in patients with biomarker selected solid tumors including prostate cancer, renal and non-small cell lung cancer (NSCLC),” continued Dr. Walters. “The ADPORT-601 trial includes plans to also evaluate PORT-7, our adenosine 2B receptor (A2BR) antagonist, and is designed to adapt over time, including safety and efficacy cohorts for both candidates as monotherapy and in combination with checkpoint inhibitors as well as other immune activating agents from Portage’s pipeline. Recently, having chaired a new conference focused on the adenosine pathway, we were encouraged to see the work many companies are doing in this space. We remain confident in our highly differentiated assets and development strategy as clinical trial sites continue to open in the U.S., to accelerate patient accrual in our clinical programs.” Company Highlights Entered into a clinical collaboration agreement with Merck for the evaluation of PORT-2, in combination with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, for patients with first-line as well as PD-1 refractory NSCLC.The Company hosted a Key Opinion Leader webinar highlighting the potential of targeting the adenosine pathway, featuring Lawrence Fong, M.D., from The University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, and Sumit Subudhi, M.D., Ph.D., from MD Anderson Cancer Center. The event covered the immunologic rationale and current clinical landscape that set the foundation for Portage’s development approach. A replay of the event is available here. Financial Results from Year Ended March 31, 2023 The Company generated a net loss of approximately $104.7 million and other comprehensive loss of approximately $109.9 million during the year ended March 31, 2023 (“Fiscal 2023”), which includes approximately $88.0 million of net non-cash expenses compared to a net loss and comprehensive loss of approximately $19.2 million during the year ended March 31, 2022 (“Fiscal 2022”), an increase in net loss of $85.5 million and an increase in other comprehensive loss of $90.7 million, year-over-year. The increase was primarily due to non-cash losses on impairment relating to the Company’s identifiable intangible assets, goodwill, and certain investments and convertible note receivable. Operating expenses, which include research and development (“R&D”) costs and general and administrative (“G&A”) expenses, were $16.6 million in Fiscal 2023, compared to $15.6 million in Fiscal 2022, an increase of $1.0 million due primarily to the addition and start of the PORT-6 clinical trial and the iNKT clinical trial for PORT-2, which is discussed more fully below. R&D costs increased by approximately $1.4 million, or approximately 21%, from approximately $6.8 million in Fiscal 2022, to approximately $8.2 million in Fiscal 2023. The increase was primarily attributable to the start-up and manufacturing costs associated with the adenosine assets (PORT-6 and PORT-7) acquired in the Tarus acquisition of $1.9 million and the clinical trial costs of $1.5 million associated with the iNKT clinical trial for PORT-2. There were no such costs incurred in Fiscal 2022. Additionally, the Company incurred additional R&D service costs totaling $0.4 million in Fiscal 2023. These increases were partially offset by a reduction in non-cash share-based compensation expense of $2.4 million with respect to stock options to purchase ordinary shares granted to employees, which was attributable to (a) the vesting over time of a portion of prior year grants; and (b) the decrease in the fair value of grants of stock options made in Fiscal 2023, as well as the timing of the grants. G&A expenses decreased by approximately $0.4 million, or approximately 5%, from approximately $8.8 million in Fiscal 2022, to approximately $8.4 million in Fiscal 2023. Professional fees increased by $1.3 million, of which $0.8 million was attributable to legal fees associated with the Tarus acquisition and $0.5 million was attributable to audit and accounting related expenses and filing fees in Fiscal 2023 associated with the updating of public filings, as well as costs associated with the Tarus acquisition review and to the iOx purchase of the then existing non-controlling interest. Payroll-related and board expenses increased by $1.1 million due to the adoption of a compensation program in Fiscal 2023 designed to attract and retain management and board members, which was partially offset by a decrease in non-cash share-based compensation expense of $2.4 million attributable to the vesting of certain stock options granted in prior years and lower fair value associated with more recent grants and the decrease of $0.4 million associated with D&O insurance, which was attributable to a decrease in the D&O premium market year-over-year. The Company’s other items of income and expense were substantially non-cash in nature and aggregated approximately $105.9 million net expense in Fiscal 2023, compared to approximately $0.8 million net income in Fiscal 2022. The primary reason for the year-over-year difference in other items of income and expense were the non-cash losses on impairment relating to the carrying value of in-process research and development (“IPR&D”) for iOx and Tarus of $59.320 million and $4.585 million, respectively, the impairment of goodwill totaling $43.862 million, and the loss on impairment relating to our investment in Stimunity and the Stimunity convertible note of $0.607 million and $0.211 million, respectively. The impairment analysis was undertaken as a result of indications of impairment from the overall life sciences market and our market capitalization. We considered a number of factors relating to the fair value analysis of the assets as of March 31, 2023, including the cost of capital, discount rates, and the impact of timing delays of obtaining data. These losses were slightly offset by non-cash gains from the change (decrease) in fair value of the deferred purchase price payable to the former Tarus shareholders and the deferred obligation - iOx milestone totaling $2.711 million and net interest income, net from investments in short-term investments in Fiscal 2023. Additionally, the Company recognized a non-cash net deferred income tax benefit of $17.9 million in Fiscal 2023, compared to the prior year, primarily attributable to the tax effect of the non-cash loss on impairment on the IPR&D in iOx , as well as changes related to the future U.K. tax rates and the effect of the change in exchange rates on the liability settleable in British pound sterling. Finally, in Fiscal 2023, the Company also performed a fair value analysis on its investment in Intensity Therapeutics, Inc. (“Intensity”) (NASDAQ: INTS), and determined a fair value of $2.087 million, as compared to its original carrying value of $7.409 million, resulting in a non-cash unrealized loss in value in Intensity of $5.322 million recorded as other comprehensive income (loss) in Fiscal 2023. As of March 31, 2023, the Company had cash and cash equivalents of approximately $10.5 million and total current liabilities of approximately $1.9 million. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. LLC., Rahway, N.J., USA. About Portage Biotech Inc. Portage is a clinical-stage immuno-oncology company advancing multi-targeted therapies to extend survival and significantly improve the lives of patients with cancer. Lead programs in the Portage portfolio include first-in-class invariant natural killer T cell (iNKT) small molecule engagers and potentially best-in-class adenosine antagonists. These programs are being advanced using innovative trial designs and translational data to identify the patient populations most likely to benefit from treatment. The Company’s unique business model leverages a strong network of academic experts and large pharma partners to rapidly and efficiently advance multiple products. For more information, please visit www.portagebiotech.com, follow us on Twitter at @PortageBiotech or find us on LinkedIn at Portage Biotech Inc. Forward-Looking Statements All statements in this news release, other than statements of historical facts, including without limitation, statements regarding about the Company’s information that are forward-looking in nature and, business strategy, plans and objectives of management for future operations and those statements preceded by, followed by or that otherwise include the words "believe," "expects," "anticipates," "intends," "estimates," “will,” “may,” “plan,” “potential,” “continue,” or similar expressions or variations on such expressions are forward-looking statements. For example, statements regarding the Company's plans to advance first-in-class therapies to improve long-term treatment response and quality of life in patients with evasive cancers; the Company’s ability to accelerate accrual in all of its clinical programs as it activates numerous sites across multiple U.S. cities and abroad; the Company’s plans to advance its clinical programs, including it iNKT engager and adenosine programs; the Company’s confidence in its highly differentiated assets and development strategy; are forward-looking statements. As a result, forward-looking statements are subject to certain risks and uncertainties, including, but are not limited to: the Company's plans and ability to develop and commercialize product candidates and the timing of these development programs; the Company's clinical development of its product candidates, including the results of current and future clinical trials; the benefits and risks of the Company's product candidates as compared to others; the Company's maintenance and establishment of intellectual property rights in its product candidates; the Company's ability to obtain financing in the future to cover its operational costs and progress its plans for clinical development, its estimates regarding its capital requirements, and its ability to continue as a going concern; the Company’s estimates of future revenues and profitability; the Company's estimates of the size of the potential markets for its product candidates; its selection and licensing of product candidates; and other factors set forth in “Item 3 - Key Information-Risk Factors” in the Company’s Annual Report on Form 20-F for the year ended March 31, 2023. Although the Company believes that the expectations reflected in these forward-looking statements are reasonable, undue reliance should not be placed on them as actual results may differ materially from these forward-looking statements. The forward-looking statements contained in this news release are made as of the date hereof, and the Company undertakes no obligation to update publicly or revise any forward-looking statements or information, except as required by law. FOR MORE INFORMATION, PLEASE CONTACT: Investor RelationsChuck Padala chuck@lifesciadvisors.com Media RelationsRaena Minarmina@lifescicomms.com ---tables to follow--- Portage Biotech Inc.Condensed Consolidated Interim Statements of Operations and Other Comprehensive Income (Loss)(U.S. Dollars in thousands, except per share amounts) Years Ended March 31, 2023 2022 2021 Expenses Research and development$8,214 $6,769 $7,312 General and administrative expenses 8,361 8,819 5,128 Loss from operations (16,575) (15,588) (12,440)Change in fair value of deferred purchase price payable - Tarus and deferred obligation - iOx milestone 2,711 – – Impairment loss - iOx IPR&D (59,320) – – Impairment loss - Tarus IPR&D (4,585) – – Impairment loss - Goodwill (43,862) Impairment loss - Stimunity (818) Share of loss in associate accounted for using equity method (260) (62) (490)Change in fair value of warrant liability 33 852 (790)Loss on equity issued at a discount – – (1,256)Loss on extinguishment of notes payable – – (223)Gain on sale of marketable equity securities – – 72 Gain on disposition of subsidiaries – – 412 Foreign exchange transaction (loss) gain (53) 24 – Depreciation expense (1) – – Interest income 217 – – Interest expense (9) (43) (177)Loss before provision for income taxes (122,522) (14,817) (14,892)Income tax benefit (expense) 17,856 (4,352) (2,297)Net loss (104,666) (19,169) (17,189)Other comprehensive income (loss) Net unrealized loss on investments (5,283) – – Total comprehensive loss for year$(109,949)$(19,169)$(17,189) Net loss attributable to: Owners of the Company$(104,611)$(16,870)$(15,833)Non-controlling interest (55) (2,299) (1,356)Net loss$(104,666)$(19,169)$(17,189) Comprehensive loss attributable to: Owners of the Company$(109,894)$(16,870)$(15,833)Non-controlling interest (55) (2,299) (1,356)Total comprehensive loss for year$(109,949)$(19,169)$(17,189) Loss per share Basic and diluted$(6.49)$(1.29)$(1.35) Weighted average shares outstanding Basic and diluted 16,119 13,060 11,733 Portage Biotech Inc. Condensed Consolidated Interim Statements of Financial Position (U.S. Dollars in thousands) March 31, 2023 2022 Assets Current assets Cash and cash equivalents$10,545 $23,352 Prepaid expenses and other receivables 2,689 1,480 Convertible note receivable 442 – Total current assets 13,676 24,832 Non-current assets Investment in associate 806 1,673 Investment in private company 2,087 7,409 Goodwill – 43,324 In-process research and development 81,683 117,388 Deferred commitment fee 839 – Other assets, including equipment, net 38 36 Total non-current assets 85,453 169,830 Total assets$99,129 $194,662 Liabilities and Equity Current liabilities Accounts payable and accrued liabilities$1,865 $750 Warrant liability – 33 Total current liabilities 1,865 783 Non-current liabilities Deferred tax liability 10,564 28,445 Deferred purchase price payable – Tarus 7,179 – Deferred obligation - iOx milestone 4,126 – Total non-current liabilities 21,869 28,445 Total liabilities 23,734 29,228 Shareholders’ Equity Capital stock 218,782 158,324 Stock option reserve 21,204 16,928 Accumulated other comprehensive (loss) income (4,325) 958 Accumulated deficit (159,616) (55,005)Total equity attributable to owners of the Company 76,045 121,205 Non-controlling interest (650) 44,229 Total equity 75,395 165,434 Total liabilities and equity$99,129 $194,662 Commitments and Contingent Liabilities