On May 27, 2024 Astrazeneca reported that high-level overall survival (OS) results from the TROPION-Lung01 Phase III trial, which previously met the dual primary endpoint of progression-free survival (PFS), numerically favoured datopotamab deruxtecan (Dato-DXd) compared to docetaxel in the overall trial population of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated with at least one prior line of therapy (Press release, AstraZeneca, MAY 27, 2024, View Source [SID1234643720]). Survival results did not reach statistical significance in the overall trial population. In the prespecified subgroup of patients with nonsquamous NSCLC, datopotamab deruxtecan showed a clinically meaningful improvement in OS compared to docetaxel, the current standard-of-care chemotherapy.

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The final analysis of OS builds on the positive progression-free survival (PFS) results presented at the 2023 European Society for Medical Oncology Congress which showed datopotamab deruxtecan demonstrated a statistically significant improvement in PFS in the overall trial population and a clinically meaningful PFS benefit in patients with nonsquamous NSCLC. In TROPION-Lung01, patient enrolment by tumour histology was balanced across treatment arms and consistent with real-world incidence with approximately 75% of patients having nonsquamous NSCLC.1,2

The safety profile of datopotamab deruxtecan in TROPION-Lung01 was consistent with the previous analysis including fewer dose reductions or discontinuations due to adverse events compared to docetaxel, and no new safety concerns identified. No new interstitial lung disease events of any grade were adjudicated as drug-related.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "Datopotamab deruxtecan is the only investigational therapy to show a clinically meaningful survival improvement in patients with previously treated nonsquamous non-small cell lung cancer versus docetaxel, which has long been unsurpassed in this post-targeted treatment and post-immunotherapy setting. These results reinforce the potential for datopotamab deruxtecan to replace conventional chemotherapy in this late-line setting and underscore our confidence in ongoing trials evaluating this therapy in first-line lung cancer."

Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: "The improvement in overall survival seen with datopotamab deruxtecan coupled with the previously reported clinically meaningful progression-free survival, more than doubling of overall response and prolonged duration of response compared to docetaxel suggest that this TROP2-directed antibody drug conjugate could potentially become an important new treatment for patients with nonsquamous non-small cell lung cancer in this advanced setting. These data will support our ongoing discussions with regulatory authorities globally to potentially bring datopotamab deruxtecan to patients as quickly as possible and mark another step forward in creating new standards of care for patients with cancer."

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo.

The data will be presented at a forthcoming medical meeting and will support regulatory applications currently under review globally, including in the US and EU for the treatment of adult patients with locally advanced or metastatic nonsquamous NSCLC who have received prior systemic therapy.

Notes

Advanced non-small cell lung cancer

Nearly 2.5 million lung cancer cases were diagnosed globally in 2022.3 NSCLC is the most common type of lung cancer, accounting for about 80% of cases.4 Approximately 75% and 25% of NSCLC tumours are of nonsquamous or squamous histology, respectively.1 While immunotherapy and targeted therapies have improved outcomes in the 1st-line setting, most patients eventually experience disease progression and receive chemotherapy.5-7 For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC, despite limited effectiveness and known side effects.5-7

TROP2 is a protein broadly expressed in the majority of NSCLC tumours.8 There is currently no TROP2-directed ADC approved for the treatment of lung cancer.9,10

TROPION-Lung01

TROPION-Lung01 is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0mg/kg) versus docetaxel (75mg/m2) in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. Patients with actionable genomic alterations were previously treated with platinum-based chemotherapy and an approved targeted therapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.

The dual primary endpoints of TROPION-Lung01 are PFS as assessed by blinded independent central review (BICR) and OS. Key secondary endpoints include investigator-assessed PFS, objective response rate, duration of response, time to response, disease control rate as assessed by both BICR and investigator, and safety.

TROPION-Lung01 enrolled approximately 600 patients in Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov.

Datopotamab deruxtecan (Dato-DXd)

Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanised anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

A comprehensive global clinical development programme is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer and HR-positive, HER2-negative breast cancer.

On May 27, 2024 MediLink Therapeutics (Suzhou) Co., Ltd. ("MediLink"), a clinical-stage biotech company, reported a new strategic collaboration with BioNTech SE (Nasdaq: BNTX, "BioNTech"), a next-generation immunotherapy company pioneering novel therapies for cancer and other serious diseases, under which BioNTech will receive an exclusive option to an exclusive global license to apply MediLink’s TMALIN antibody-drug conjugate (ADC) platform, for several novel targets chosen by BioNTech (Press release, Suzhou Medilink Therapeutics, MAY 27, 2024, View Source [SID1234643719]).

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Under the terms of this new agreement, MediLink will receive an upfront payment of $25 million and is eligible to receive additional development, regulatory and sales milestone payments potentially totaling up to $1.8 billion, as well as tiered royalties on potential future global annual net sales. As part of the agreement, MediLink will hold the right of first negotiation for future collaboration of these ADC product candidates if BioNTech wishes to exclusively license or assign rights in such ADC product candidates solely on the Mainland China market or Mainland China market together with one or more of the markets including of Hong Kong Special Administrative Region (SAR), Macau SAR or Taiwan region.

In October 2023, MediLink and BioNTech entered into a strategic collaboration and global license agreement to develop BNT326/YL202, a next-generation anti-HER3 ADC. Both parties have decided to expand their collaboration and have reached this new platform collaboration license agreement.

The expansion of the collaboration marks a further consolidation of the strategic partnership between MediLink and BioNTech, laying a new foundation for the mutual R&D collaboration in the ADC field.

On May 27, 2024 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CANF), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address oncological and inflammatory diseases, reported that its VP of Business Development, Dr. Sari Fishman, will hold 23 partnering meetings with Biotech & Pharma companies, who showed interest in partnering with Can-Fite (Press release, Can-Fite BioPharma, MAY 27, 2024, View Source [SID1234643718]). The meetings will take place during the Bio International Convention 2024 in San Diego, USA, on June 3-6. View Source;gclid=Cj0KCQjwu8uyBhC6ARIsAKwBGpR1uawA2qpi9I2O3htc7bwxwiKsbpmP1IefbWC8KrkYc5njVnODEpYaAsWWEALw_wcB

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Can-Fite currently has out-licensing and distribution deals with seven pharma companies across North America, Europe, and Asia, which include upfront and milestone payments. The Company’s growing slate of indications and advanced pipeline are attracting increased interest from additional potential partners that will attend the conference in San Diego. Focusing on its core expertise in clinical development, Can-Fite pursues a strategy of partnering with companies in specific geographic markets that specialize in pharmaceutical distribution and regional regulatory approval.

Can-Fite’s pipeline of indications includes the two small molecule orally bioavailable drugs, Piclidenoson positioned for the treatment of Psoriasis (Phase 3) and Namodenoson for the treatment of advance liver cancer (Phase 3), pancreatic cancer (Phase 2a) and MASH (Phase 2b).

On May 27, 2024 The U.S. Food and Drug Administration (FDA) reported that it has accepted for Priority Review the supplemental Biologics License Application (sBLA) for the investigational use of Sarclisa (isatuximab) in combination with bortezomib, lenalidomide and dexamethasone (VRd) for the treatment of patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) (Press release, Sanofi, MAY 27, 2024, View Source [SID1234643717]). If approved, Sarclisa would be the first anti-CD38 therapy in combination with standard-of-care VRd in newly diagnosed patients not eligible for transplant, which would be the third indication for Sarclisa in multiple myeloma. The target action date for the FDA decision is September 27, 2024. A regulatory submission is also under review in the European Union (EU).

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Dietmar Berger, M.D., Ph.D.
Chief Medical Officer, Global Head of Development at Sanofi
"Despite recent advancements in multiple myeloma treatment, there remains a significant unmet need for new frontline therapies, particularly for transplant-ineligible patients who can face poor outcomes from the disease. The filing acceptances, as well as the FDA’s Priority Review designation, reinforce our confidence in Sarclisa as a potential best-in-class treatment and represent a critical step toward advancing this combination in a difficult-to-treat cancer."

The sBLA, as well as the submission in the EU, is based on positive results from the IMROZ phase 3 clinical study evaluating the investigational use of Sarclisa in combination with standard-of-care VRd. In December 2023, the study met its primary endpoint at a planned interim analysis for efficacy, demonstrating statistically significant improvement in progression-free survival (PFS) with Sarclisa in combination with VRd compared with VRd alone in transplant-ineligible patients with NDMM. The safety and tolerability of Sarclisa observed in this study was consistent with the established safety profile of Sarclisa and VRd.

The IMROZ study is the fourth phase 3 study investigating Sarclisa combinations in NDMM patients to show superiority versus standard-of-care VRd and KRd, reinforcing its best-in-class potential. Results from the IMROZ study will also be featured during an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and during the plenary scientific session at the 2024 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress.

Priority Review is granted to regulatory applications seeking approval for therapies that have the potential to provide significant improvements in the treatment, diagnosis or prevention of serious conditions.

The investigational use of Sarclisa in combination with VRd in patients with transplant-ineligible NDMM is currently under clinical development, and its safety and efficacy for this indication have not been fully evaluated by any regulatory authority.

About the study

The global, randomized, multi-center, open-label IMROZ phase 3 clinical study enrolled 446 patients with newly diagnosed, transplant-ineligible MM across 21 countries and 104 centers. During the study, Sarclisa was administered through an intravenous infusion at a dose of 10 mg/kg once weekly for five weeks during first 42-day cycle and once every two weeks in cycles 2 to 4 in combination with subcutaneous bortezomib, oral lenalidomide and intravenous or oral dexamethasone. Then Sarclisa was administered every 2 weeks from cycle 5 to 17 and every 4 weeks in cycles 18+ during 28-day cycles in combination with lenalidomide and dexamethasone at the standard dose, until disease progression, unacceptable safety profile or patient’s decision to stop the study treatment.

The primary endpoint was progression-free survival. Key secondary endpoints include complete response rate, minimal residual disease (MRD) negativity rate for patients with a complete response, very good partial response or better rate, and overall survival. Other secondary endpoints were overall response rate, time to progression, duration of response, time to first response, time to best response, progression-free survival on next line of therapy, progression-free survival by MRD status, sustained MRD negativity greater than or equal to 12 months rate, safety, pharmacokinetic profile, immunogenicity, disease-specific and generic health-related quality of life, disease and treatment-related symptoms, health state utility, and health status.1

About Sarclisa

Sarclisa is a monoclonal antibody that binds to a specific epitope on the CD38 receptor on multiple myeloma (MM) cells, inducing distinct antitumor activity. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activities. CD38 is highly and uniformly expressed on the surface of MM cells, making it a potential target for antibody-based therapeutics such as Sarclisa.

Based on the phase 3 ICARIA-MM study, Sarclisa is approved in >50 countries, including the U.S. and EU, in combination with pomalidomide and dexamethasone for the treatment of certain patients with relapsed refractory MM (RRMM) who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor and who progressed on last therapy. Based on the phase 3 IKEMA study, Sarclisa is also approved in 50 countries in combination with carfilzomib and dexamethasone, including in the U.S. for the treatment of patients with RRMM who have received 1–3 prior lines of therapy and in the European Union for patients with MM who have received at least 1 prior therapy. In the U.S., the generic name for Sarclisa is isatuximab-irfc, with irfc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration (FDA).

Sarclisa continues to be evaluated in multiple ongoing phase 3 clinical studies in combination with current standard treatments across the MM treatment continuum. It is also under investigation for the treatment of other hematologic malignancies, and its safety and efficacy have not been evaluated by any regulatory authority outside of its approved indication.

For more information on Sarclisa clinical studies, please visit www.clinicaltrials.gov.

About multiple myeloma

Multiple myeloma (MM) is the second most common hematologic malignancy,2 with more than 180,000 new diagnoses of MM worldwide yearly.3 Despite available treatments, MM remains an incurable malignancy with an estimated 52% five-year survival rate for newly diagnosed patients.4 Since MM does not have a cure, most patients will relapse. Relapsed MM is the term for when the cancer returns after treatment or a period of remission. Refractory MM refers to when the cancer does not respond or no longer responds to therapy.

On May 27, 2024 InDex Pharmaceuticals Holding AB (publ) ("InDex Pharmaceuticals" or the "Company") reported to have entered into a conditional agreement to acquire all shares in Flerie Invest AB (Press release, InDex Pharmaceuticals, MAY 27, 2024, View Source [SID1234643716]). The acquisition is made through an issue in kind of 6,073,952,948 new shares in the Company, following which Flerie Invest AB’s shareholders will initially hold approximately 91.9 per cent of the shares and InDex Pharmaceuticals’ existing shareholders will initially hold approximately 8.1 per cent of the shares in the Company.

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The transaction in brief
InDex Pharmaceuticals has entered into an agreement with the shareholders of Flerie Invest AB ("Flerie") to acquire all shares in Flerie through an issue in kind of 6,073,952,948 new shares in the Company (the "Consideration Shares", and the "Transaction", respectively). Through the Transaction, Flerie will become a wholly-owned subsidiary of InDex Pharmaceuticals and Flerie’s shareholders will initially hold approximately 91.9 per cent of the total number of shares and votes in the Company, prior to the completion of the Capital Raise (as defined below). As a result of the Transaction, the Company will change its name to Flerie AB ("New Flerie").
Flerie is valued at approximately SEK 3,073 million in the Transaction, based on reported net asset value as of 31 March 2024 with a discount of 10 per cent. InDex Pharmaceuticals is valued at approximately SEK 269 million, corresponding to the Company’s estimated cash position after closing costs with a premium of 20 per cent, which entails a subscription price of approximately SEK 0.506 per Consideration Share.
As part of the Transaction and the continued financing of New Flerie, a number of institutional investors, including the Company’s existing shareholders the Fourth Swedish National Pension Fund, HBM Healthcare Investments, Linc AB and SEB Stiftelsen, have undertaken to subscribe for new shares in the Company in a directed share issue (the "Capital Raise"). Through the Capital Raise, the Company will raise in aggregate approximately MSEK 520 before transaction costs.
The Company intends to convene an Extraordinary General Meeting to be held on 10 June 2024, at 8:30 a.m. CEST, to resolve on approval of the Transaction, issue in kind of the Consideration Shares, authorization to issue shares for the Capital Raise, election of new Board members and auditor, and other resolutions that follow from the Transaction (the "Second EGM"). On 6 May 2024 the Company convened an Extraordinary General Meeting to be held on the same day, 10 June 2024 at 8:00 a.m. CEST, to resolve on the amendments to the articles of association that follow from the Transaction (the "First EGM", and together with the Second EGM, the "EGMs").
HBM Healthcare Investments, Linc AB, SEB Stiftelsen and S-E Bankens Utvecklingsstiftelse, who together represent approximately 27.9 per cent of the shares and votes in InDex Pharmaceuticals, have undertaken to vote in favour of the Transaction and related resolutions at the EGMs. Furthermore, the Fourth Swedish National Pension Fund, representing approximately 9.8 per cent of the shares and votes in the Company, has expressed its intention to vote in favour of the Transaction and related resolutions at the EGMs.
The completion of the Transaction is, among other things, conditional upon resolutions at the EGMs and that the Company receives approval for continued listing on Nasdaq First North Growth Market.
Further information about the Transaction, Flerie and New Flerie will be set out in a company description that is expected to be published no later than 27 May 2024.
Background and motive
Following the discontinuation of cobitolimod development and InDex Pharmaceuticals announcing that the Company will not continue the development of any of its other compounds, various options for the Company’s future have been evaluated to maximize shareholder value. This has resulted in the proposed Transaction.

Jenny Sundqvist, CEO of InDex Pharmaceuticals.
"I am very pleased that the evaluation has resulted in the proposed Transaction, as Flerie came out as the best option. Flerie has a highly regarded Board and management with excellent track record​ and a balanced risk profile. The attractive deal terms include a possibility for share redemption, in addition to being able to trade which ensures that we can offer shareholders optionality".

Ted Fjällman, CEO of Flerie and intended CEO of New Flerie.
"This broadening of our shareholder base and becoming listed is a key step in Flerie’s plan to create a new model for life science investing: We continue our long-term, active investment strategy, while offering new shareholders access to and liquidity in difficult-to-assess biotech companies. The Transaction and the Capital Raise allow accelerated development of a risk-diversified portfolio of product development and commercial growth companies spanning obesity, diabetes, heart disease, cancer and autoimmune disorders to pharmaceutical manufacturing services, diagnostics, medical devices and tools".