On August 5, 2022 PharmaMar (MSE:PHM) reported that Zepzelca (lurbinectedin) has received the Innovation Passport (Innovative Medicine Designation) by the MHRA (UK Medicines and Healthcare products Regulatory Agency) (Press release, PharmaMar, AUG 5, 2022, View Source [SID1234617672]).

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The MHRA’s Innovative Licensing and Access Pathway (ILAP) aims to accelerate the time to market, facilitating patient access to medicines. The ILAP comprises as the first step an "Innovation Passport" designation which supports innovative approaches to the safe, timely and efficient development of medicines to improve patient access. The criteria for the innovation passport include where the condition is life-threatening or seriously debilitating, or where there is a significant patient or public health need and where the medicinal product has the potential to offer benefits to patients (improved efficacy or safety, improved patient care or quality of life as compared to alternative therapeutic options).

Ali Zeaiter, M.D., VP Clinical Development & Regulatory Affairs of PharmaMar, said: "Lurbinectedin is an innovative medicine that showed clinical benefit for patients with relapsed Small Cell Lung Cancer (SCLC) and obtained provisional approvals in a number of countries (including USA, Canada and Australia) and is being developed in other clinically significant indications. SCLC represents an unmet medical need in the UK and worldwide, and our objectives are aligned with those of the UK public health authorities to facilitate and improve patients access to medicines such as lurbinectedin," and added: "We believe that the innovation passport designation is an important step towards facilitating SCLC patients’ access to a new treatment option."

On May 4th 2022, PharmaMar announced it had submitted a conditional marketing authorization application to the UK’s MHRA for the treatment with lurbinectedin in adult patients with metastatic Small Cell Lung Cancer who have progressed following prior platinum-based chemotherapy based on data from the Phase II basket trial with lurbinectedin in monotherapy. PharmaMar expects a response to such application by the end of this year or first quarter of 2023. In addition, the LAGOON Phase III trial could be used as a confirmatory trial.

On 2020 PharmaMar and Immedica Pharma AB signed an agreement for the exclusive distribution and marketing of lurbinectedin for the UK and other territories.

On August 5, 2022 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported new preclinical data supporting the potential best-in-class profile of NVL-655 – an ALK-selective inhibitor, and a "Trial in Progress" poster for the Phase 1/2 ARROS-1 study of NVL-520 – a ROS1-selective inhibitor (Press release, Nuvalent, AUG 5, 2022, View Source [SID1234617668]). NVL-520 and NVL-655 are central nervous system (CNS)-penetrant kinase inhibitors designed to specifically solve for the dual challenges of kinase resistance and selectivity commonly observed with currently available inhibitors.

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The two posters will be presented at the IASLC 2022 World Conference on Lung Cancer (WCLC) Annual Meeting taking place August 6-9, 2022 in Vienna, Austria. The posters will also be available on the Nuvalent website.

"Our presentations at WCLC showcase the value that our collaborations with leading physician-scientists and translational investigators bring towards characterizing and developing our parallel lead programs for patients with non-small cell lung cancer (NSCLC)," said James Porter, Ph.D., Chief Executive Officer of Nuvalent. "We are grateful for our continued collaborations focused on advancing the understanding of resistance to kinase inhibitors, as well as the dedication and support of the Phase 1 clinical investigators participating in our ongoing studies for patients with advanced NSCLC and other solid tumors."

"We selected NVL-520 and NVL-655 based on the demonstrated strength of their preclinical profiles and their potential to drive deep, durable responses for patients with ROS1-positive and ALK-positive cancers, respectively. With both programs now under clinical investigation, we remain committed to continued, rigorous preclinical characterization to both deepen our understanding of our programs as well as to support the advancement of tools and models that may help accelerate the development of new therapies for genomically-driven cancers," said Henry Pelish, Ph.D., Vice President of Biology at Nuvalent. "We are pleased to share data further characterizing NVL-655 in a new patient-derived model of lorlatinib-resistant ALK-positive NSCLC with the treatment-emergent G1202R/T1151M compound resistance mutation, developed by our clinical and translational collaborators at Gustave Roussy."

The MR448re patient-derived model was established from cancer cells retrieved from a NSCLC patient previously treated with four prior ALK kinase inhibitors and most recently progressing following treatment with lorlatinib. Presence of an EML4-ALK fusion and the G1202R/T1151M compound mutation was confirmed by sequencing.

"The rapid development of the MR448re patient-derived model and subsequent evaluation of NVL-655 is a testament to the efficient cooperation between our clinical and translational investigators, and our collaborators at Nuvalent," said Luc Friboulet, Ph.D., investigator at Gustave Roussy. "NVL-655 showed strong antitumor activity in this heavily refractory model, while lorlatinib showed limited inhibitory activity consistent with treatment history. This further supports the differentiating and potentially best-in-class preclinical profile of NVL-655, which has previously demonstrated the ability to retain activity in the presence of a broad spectrum of single and compound ALK resistance mutations while maintaining a wide selectivity window over TRKB."

A "Trial in Progress" poster summarizing the preclinical profile of NVL-520 and clinical trial design of the Phase 1/2 ARROS-1 study (NCT05118789) for NVL-520 will also be presented. This multicenter, open-label, dose-escalation and expansion trial is designed to evaluate NVL-520 as an oral monotherapy for patients with advanced ROS1-positive NSCLC and other solid tumors. The ongoing Phase 1 dose-escalation portion of the study is currently enrolling ROS1-positive NSCLC patients who have previously received at least one ROS1 TKI, or patients with other ROS1-positive solid tumors previously treated with any prior therapy. Nuvalent plans to share preliminary dose-escalation data from ARROS-1 in the second half of 2022.

WCLC Presentation Overview:

Title: Preclinical Activity of NVL-655 in a Patient-Derived NSCLC Model with Lorlatinib-Resistant ALK G1202R/T1151M Mutation
Authors: H. Mizuta1, L. Bigot1, A. Tangpeerachaikul2, H.E. Pelish2, L. Friboulet1
Abstract Number: EP08.02-020
Session Category: Metastatic Non-small Cell Lung Cancer
Session Title: Molecular Targeted Treatments
Session Date and Time: August 7, 2022, 9:45am – 6:00pm CEST

1Gustave-Roussy, Villejuif, France; 2Nuvalent, Inc., Cambridge, MA, USA

Summary of Presentation:

ALK G1202R single and compound mutations are recurrent mechanisms of resistance to previous-generation therapies, including alectinib and lorlatinib.
NVL-655 showed strong antitumor activity in preclinical models derived from ALK positive patients who have progressed on treatment with earlier-generation ALK inhibitors, including a G1202R/T1151M compound mutation model derived from a patient previously treated with crizotinib, alectinib, brigatinib, and lorlatinib.
Among all inhibitors tested, NVL-655 continues to show the broadest activity across ALK fusion partners and resistance mutations while maintaining a wide selectivity window over TRKB.
NVL-655 is currently being evaluated in the Phase 1/2 ALKOVE-1 study for patients with advanced ALK+ NSCLC and other solid tumors, including those with ALK resistance mutations and CNS metastases (NCT05384626).
Title: NVL-520, a Highly Selective ROS1 Inhibitor, in Patients with Advanced ROS1-Positive Solid Tumors: The Phase 1/2 ARROS-1 Study
Authors: A. Drilon1, S-H.I. Ou2, S. Gadgeel3, M. Johnson4, A. Spira5, G. Lopes6, B. Besse7, E. Felip8, A.J. van der Wekken9, A. Calles10, M.J. de Miguel11, D.R. Camidge12, Y. Elamin13, S. Liu14, J. Bauman15, D. Haggstrom16, G. Riley17, H.E. Pelish17, V.W. Zhu17, J.J. Lin18
Abstract Number: EP08.02-041
Session Category: Metastatic Non-small Cell Lung Cancer
Session Title: Molecular Targeted Treatments
Session Date and Time: August 7, 2022, 9:45am – 6:00pm CEST

1Memorial Sloan Kettering Cancer Center, New York/NY/USA ,2University Of California Irvine Medical Center, Orange/CA/USA ,3Henry Ford Cancer Institute, Detroit/MI/USA ,4Sarah Cannon Research Institute, Nashville/TN/USA,5NEXT Oncology – Virginia Cancer Specialists, Fairfax/VA/USA ,6Sylvester Comprehensive Cancer Center at the University of Miami and the Miller School of Medicine, Miami/FL/USA ,7Institut Gustave Roussy, Villejuif Cedex/FR,8Hospital Vall d’Hebron, Barcelona/ES ,9University of Groningen, University Medical Centre Groningen,Groningen/NL ,10Hospital Universitario Gregorio Marañón, Madrid/ES ,11START Madrid-HM CIOCC, Madrid/ES,12University of Colorado Cancer Center, Anschutz Medical Campus, Aurora/CO/USA ,13MD Anderson Cancer Center, Houston/TX/USA ,14Georgetown University, Washington/DC/USA ,15Fox Chase Cancer Center, Philadelphia/PA/USA,16Levine Cancer Institute, Atrium Health, Charlotte/NC/USA ,17Nuvalent, Inc., Cambridge/MA/USA ,18Massachusetts General Hospital, Boston/MA/USA

Summary of Presentation:

NVL-520 has demonstrated CNS activity and potent and selective inhibition of ROS1 & ROS1 G2032R over TRKB in preclinical models. These data indicate the potential to minimize TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and drive more durable responses for patients with ROS1+ tumors, including those with ROS1 resistance mutations and CNS metastases.
ARROS-1 is a Phase 1/2 study evaluating the safety and activity of NVL-520 in patients with advanced ROS1+ NSCLC and other solid tumors, including those with ROS1 resistance mutations and CNS metastases.
The Phase 1 portion of the study is open and actively enrolling in the USA, Spain, the Netherlands, and France, with further global expansion planned.
Phase 2 cohorts are designed to support potential registration in TKI-naive or previously treated ROS1+ NSCLC.
About NVL-655

NVL-655 is a novel brain-penetrant ALK-selective inhibitor created to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with the solvent front G1202R mutation or compound mutations G1202R / L1196M ("GRLM"), G1202R / G1269A ("GRGA"), or G1202R/L1198F ("GRLF"). NVL-655 has been optimized for CNS penetrance to improve treatment options for patients with brain metastases. NVL-655 has been observed in preclinical studies to selectively inhibit wild-type ALK and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and drive more durable responses for patients. NVL-655 is currently being investigated in the ALKOVE-1 study (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors.

About NVL-520

NVL-520 is a novel brain-penetrant ROS1-selective inhibitor designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with the prevalent G2032R resistance mutation and those with the S1986Y/F, L2026M, or D2033N resistance mutations. NVL-520 has been optimized for brain penetrance to potentially improve treatment options for patients with brain metastases. NVL-520 has been observed in preclinical studies to selectively inhibit wild-type ROS1 and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and drive more durable responses for patients. NVL-520 is currently being investigated in the ARROS-1 study (NCT05118789), a first-in-human Phase 1/2 clinical trial for patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors.

On August 5, 2022 Immunome, Inc. (Nasdaq: IMNM), a biopharmaceutical company that utilizes its human memory B cell platform to discover and develop first-in-class antibody therapeutics, reported financial results for the second quarter ended June 30, 2022 and provided a corporate update (Press release, Immunome, AUG 5, 2022, View Source [SID1234617667]).

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"The second quarter marked our transition into a clinical stage company, as we continue to dose patients in our Phase 1b study of our COVID-19 antibody cocktail, IMM-BCP-01," stated Purnanand Sarma, Ph.D., President and CEO of Immunome. "We also presented data in the second quarter that demonstrated the retention of neutralizing activity against the BA.4/.5, and BA.2.12.1 subvariants of SARS CoV-2. We look forward to reporting topline results from our Phase 1b study of IMM-BCP-01 in the second half of this year."

Dr. Sarma continued, "Additionally, we continue to make strides with our lead oncology candidate, IMM-ONC-01. Through an extensive profiling assessment of IL-38 mRNA using a database1 of over 60 cancer subtypes, we concluded that IL-38 is overexpressed in multiple cancers of high clinical unmet need. We are excited to continue advancing IMM-ONC-01 towards IND submission, as we believe IL-38 represents a promising target in multiple tumor types."

Highlights

IMM-BCP-01 Retains Neutralizing Activity Against Prevalent Omicron Subvariants, BA.4/.5 and BA.2.12.1. In July 2022, Immunome announced that its antibody cocktail retained activity against the BA.4/.5 and BA.2.12.1 subvariants in pseudovirus testing. Data recently published in the peer-reviewed journal Science Immunology provides a mechanistic basis for how IMM20253 binding, which is conserved across all variants to date including Omicron and its sub-lineages, neutralized SARS-CoV-2.
Initiation of Phase 1b Study of IMM-BCP-01 for the Treatment of COVID-19. In June 2022, Immunome announced the first patient had been enrolled in a clinical trial of IMM-BCP-01, a three-antibody cocktail for the treatment of SARS-CoV-2. Immunome currently expects to announce topline data in the second half of this year.
Research & Development Update on Lead Oncology Candidate Targeting IL-38. In May of 2022, Immunome announced updates to the ongoing development of its lead oncology program, IMM-ONC-01, specifically on mRNA expression profiling and collaboration with Fox Chase Cancer Center.
Financial Highlights

Research and development (R&D) expenses: R&D expenses for the three months ended June 30, 2022 were $5.7 million.
General and administrative (G&A) expenses: G&A expenses for the three months ended June 30, 2022 were $3.2 million.
Net loss: Net loss for the three months ended 2022 was $8.9 million.
Cash and cash equivalents: As of June 30, 2022, cash and cash equivalents totaled $34.6 million.
The investigational work related to IMM-BCP-01 was funded by the U.S. Department of Defense’s (DOD) Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) in collaboration with the Defense Health Agency (DHA) (Contract number: W911QY-20-9-0019).

[1] Tempus RealWorld Data

On August 5, 2022 BioNTech SE (Nasdaq: BNTX, "BioNTech") and Genmab A/S ("Genmab") reported an expansion of their global strategic collaboration to develop and commercialize novel immunotherapies for the treatment of cancer patients (Press release, BioNTech, AUG 5, 2022, View Source [SID1234617666]). Under this expansion, BioNTech and Genmab will jointly work to research, develop and commercialize novel monospecific antibody candidates for various cancer indications. Since 2015, the companies have been working on the joint development of bispecific cancer antibodies aimed at improving immunotherapy options for cancer patients.

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"The expansion of our collaboration with Genmab extends our antibody portfolio and will further strengthen our oncology pipeline in indications with high unmet medical needs," said Prof. Ugur Sahin, M.D., Chief Executive Officer and Co-Founder of BioNTech. "We are committed to working together with our colleagues at Genmab to develop new treatments for people affected by cancer."

"We are thrilled to expand our collaboration with BioNTech to include additional novel antibody therapies with the goal to deliver them to patients in need of innovative therapeutic options," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "Strategic partnerships, like our collaboration with BioNTech, are critical to developing differentiated antibody medicines with the aim of improving the lives of cancer patients."

Under the expanded collaboration, the companies will jointly develop and commercialize, subject to regulatory approval, monospecific antibodies leveraging Genmab’s proprietary HexaBody technology platform. The first monospecific antibody candidate, GEN1053/BNT313, is expected to enter clinical trials by the end of 2022. GEN1053/BNT313 is a CD27 antibody based on the HexaBody technology, specifically engineered to form an antibody hexamer (a formation of six antibodies) upon binding its target on the cell membrane of the T cells. Under the terms of the agreement, the companies will equally share the development costs and potential future profit deriving from GEN1053/BNT313.

The companies currently have two jointly developed investigational medicines in clinical testing since 2019, fusing BioNTech’s proprietary immunomodulatory antibodies and Genmab’s DuoBody technology platform: GEN1046/BNT311 is being evaluated in Phase 1/2 clinical trials for the treatment of advanced solid tumors (NCT04937153, NCT03917381), and in a Phase 2 study of patients with non-small cell lung cancer (NSCLC) (NCT05117242). GEN1042/BNT312 is being evaluated for the treatment of metastatic or locally advanced solid tumors in a Phase 1/2 study (NCT04083599).

On August 5, 2022 Ipsen S.A. (Euronext: IPN; ADR: IPSEY) reported that Hibernia Merger Sub, Inc. (Purchaser), its wholly owned indirect subsidiary, has extended the expiration time for the previously announced tender offer to purchase all of the issued and outstanding shares of common stock (the Shares) of Epizyme, Inc. (NASDAQ: EPZM) (Epizyme) at a price of $1.45 per share, to the holder in cash, without interest and less applicable withholding taxes, plus one non-transferable contingent value right (CVR) per Share, until 11:59 p.m., Eastern time on Thursday 11 August 2022, unless further extended (Press release, Ipsen, AUG 5, 2022, View Source [SID1234617646]). The tender offer was previously scheduled to expire at one minute after 11:59 p.m., Eastern time, on Monday 8 August 2022. All other terms and conditions of the tender offer remain unchanged.

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Each CVR represents the right to receive one or more payments in cash, of up to $1.00 per CVR, contingent upon the achievement of certain milestones upon the terms and subject to the conditions described in the Offer to Purchase dated 12 July 2022 (together with any amendments or supplements thereto, the ‘Offer to Purchase’) and in the related Letter of Transmittal.

The tender offer was extended to allow additional time for the condition relating to the expiration or termination of the waiting period (and any extension thereof) under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 as amended (the HSR Condition), to be satisfied.

Computershare Trust Company, N.A., the depositary and paying agent for the tender offer, has indicated that, as of 5:00 p.m., Eastern time, on 4 August 2022, approximately 42,256,760 Shares had been validly tendered into and not validly withdrawn from the tender offer, representing approximately 25% of the Shares outstanding as of 6 July 2022. Stockholders who have already tendered their Shares into the tender offer do not have to re-tender their Shares or take any other action as a result of the extension of the expiration time of the tender offer.

Completion of the tender offer remains subject to additional conditions described in the Tender Offer Statement on Schedule TO (as may be amended or supplemented) filed by Purchaser, Ipsen Biopharmaceuticals, Inc., Ipsen Pharma SAS and Ipsen S.A., with the United States Securities and Exchange Commission (SEC) on 12 July 2022. Such conditions include there having been validly tendered and not validly withdrawn Shares that, considered together with all other Shares (if any) beneficially owned by Ipsen Pharma SAS and its subsidiaries, represent at least one Share more than 50% of the total number of Shares outstanding immediately prior to the expiration of the Offer (including any extensions).

Requests for documents and questions regarding the tender offer may be directed to Georgeson LLC, the Information Agent for the tender offer, by telephone (toll-free) at (866) 203-9357 or by email at [email protected].